NFL Week 5 Preview: Schedule, storylines, matchups to watch and betting spreads

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• Broncos and Eagles square off: The game features two of the NFL’s best defenses over the last two seasons.  

• A major Monday Night Showdown: The upstart Jaguars host the Chiefs in a litmus test for both sides.

Estimated Reading Time: 20 minutes

We’re diving into all 14 matchups in Week 5 of the 2025 NFL season — including key storylines, matchups to watch and injury news. The San Francisco 49ers and Los Angeles Rams kick things off on Thursday Night Football.

Click below to jump to a game:

SF@LAR | MIN@CLE | HOU@BAL | MIA@CAR | LV@IND | NYG@NO | DAL@NYJ | DEN@PHI | TEN@ARI | TB@SEA | DET@CIN | WAS@LAC | NE@BUF | KC@JAX

Storyline of the game: Injuries continue to pile up for 49ers

A short week of preparation is already a difficult task for NFL teams, one that’s been made even more challenging for the 49ers as the roster continues to suffer key injuries week after week. Chief among those concerns is the health of Brock Purdy, who returned after a two-game absence and may have reaggravated his toe issue. That alone will prove to be difficult to overcome against a Rams team that has beaten San Francisco in three consecutive meetings, and remains undefeated at home this season.   

Matchups to watch: Rams RT Rob Havenstein vs. 49ers EDGE Bryce Huff 

A mix of injuries and ineffective play have hit the Rams’ offensive line hard to start the year, particularly when it comes to pass protection. Veteran tackle Rob Havenstein has dealt with a nagging ankle injury to start the year, contributing to his 47.2 PFF-pass blocking grade. This past week, Havenstein surrendered a massive 20% pressure rate with nine pressures, tied for the most given up by any tackle in a game this season.

The 49ers’ pass rush struggled to generate pressure this past week after losing Nick Bosa for the year, totaling just a 15.2% pressure rate — a bottom-five performance among all teams this season. Bryce Huff has been one of the few bright spots in this unit, with his 23.9% pass-rush win rate ranking in the top 12. 

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Storyline of the game: Browns turn to rookie Dillon Gabriel 

After a 1-3 start to the year, Browns head coach Kevin Stefanski made the decision to sit down veteran quarterback Joe Flacco in favor of third-round rookie Dillon Gabriel. While Gabriel doesn’t possess the most acclaimed grading profile in the 2025 draft class, he was particularly strong at limiting mistakes, with his 11.5% negatively-graded throw rate per dropback ranking in the 95th percentile in college football last season.

Matchups to watch: Browns RB Quinshon Judkins vs. Vikings Front Seven

With Gabriel taking over as the starter under center, expect the Browns to lean even more heavily into the running game. Judkins has been impressive since taking a stranglehold on the backfield, with his 72.5 overall PFF grade ranking in the top 15 at the position. The first-year back is difficult to bring down, having generated the fifth-highest yards-after-contact-per-attempt average (4.2) in the NFL. 

The Vikings went into Week 3 as one of the strongest run defense units in the NFL. But aggressiveness is a double-edged sword. In Week 4, Minnesota was gashed by Kenneth Gainwell to the tune of 99 yards and two touchdowns, with 78 yards coming after first contact. 

Additional News: 

Storyline of the game: Ravens’ injuries tip the scale

Baltimore’s trouble to start the year turned from bad to worse with the news that the team will be without numerous key players on both sides of the ball. On defense, Roquan Smith and Marlon Humphrey are expected to miss multiple weeks, in addition to the crippling loss of DI Nnamdi Madubuike — who was ruled out for the rest of the season. However, the more pressing news comes with the expectation that Lamar Jackson will likely miss this game and potentially multiple weeks. 

Matchups to watch: Texans WR Christian Kirk vs. Ravens CB Keyon Martin

Since making his Texans debut in Week 3, Christian Kirk has struggled to get on the same page with his quarterback, C.J. Stroud. The new Texans receiver has hauled in just six of his 12 targets for just 45 yards, producing a 58.1 PFF receiving grade.

This may be an opportunity for Kirk to take a step forward, with Keyon Martin set to replace the injured Marlon Humphrey in the slot. The undrafted rookie is still getting acclimated to the NFL game, having generated a 59.2 PFF coverage grade. That’s due in large part to having surrendered 6.1 yards and open separation on over 85% of his coverage targets.

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Storyline of the game: Tyreek Hill out, Darren Waller in

The Dolphins experienced a tough loss with Tyreek Hill suffering a season-ending knee dislocation in Week 4. He was their highest-graded player (82.1) on either side of the ball, leaving Mike McDaniel’s offense severely hindered. On a positive note, Darren Waller’s return from the NFL — after spending 2024 in retirement — was strong. Even at 33 years old, Waller made an immediate impact, catching a pair of scores and earning an 88.8 PFF receiving grade. 

Matchups to watch: Dolphins TE Darren Waller vs. Panthers S Tre’von Moehrig & LB Christian Rozeboom

As mentioned above, Waller had a strong return to the NFL, however, it came off a very limited snap share, playing just over 27% of snaps. He saw a target on 33.3% of his 12 routes run, and if his role continues to grow, his impact on the Miami offense would be significant. 

This could be a spot for Waller to flourish against a Panthers defense that has struggled to slow down tight ends this season. Their 29.1 PFF coverage grade versus tight ends ties for the lowest in the NFL in 2025. Moehrig and Rozeboom have particularly had issues with the assignment, having surrendered a combined 11 catches for 184 yards, with the pair each falling below a 30.0 PFF coverage grade. 

Additional News: 

• Dolphins WR Tyreek Hill (knee) suffered a dislocated knee and multiple torn ligaments, will miss the remainder of the year; not guaranteed to be ready for 2026
• Dolphins CB Jason Marshall Jr. placed on IR
• Panthers RG Chandler Zavala (knee) placed on IR

Storyline of the game: Colts impress despite loss 

Despite coming away from Week 4 with their first loss of the season, the Colts have converted many onlookers into believers after a strong performance on the road against an elite Rams team. Indy went blow for blow and very well could have built a sizable lead on LA, if not for a mental error by Adonai Mitchell — fumbling a would-be 75 yard score through the back of the end zone for a turnover. Now, attention turns to a Raiders team that suffered a similarly tough setback, having their game-winning field goal attempt blocked to close out the game. 

Matchups to watch: Raiders EDGE Maxx Crosby vs. Colts RT Braden Smith

Maxx Crosby erupted in Week 4, producing his best PFF grade (91.5) in the past two years. Although Mad Maxx didn’t record a sack, he did manage to secure an interception off a batted pass he himself tipped into the air. However, he was still impressive as a pass rusher, recording a 21.9% pass-rush win rate. 

Conversely, Braden Smith struggled this past week against a potent Rams pass rush. He secured just a 41.6 PFF pass-block grade after allowing a 15% pressure rate and permitting a pair of quarterback hits. Smith will have to regain his footing quickly in this matchup with Crosby.   

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Storyline of the game: Unexpected steps forward

Both the Giants and Saints showed surprising resilience in difficult matchups in Week 4. New York captured its first win of the year against the undefeated Chargers behind an impressive defensive performance. While the Saints weren’t able to get into the win column, they put up a fight to stick with the undefeated Bills, coming within a field goal of taking the lead in the fourth quarter. While these teams have struggled to start the year, expect a tough battle fueled by momentum on both sidelines. 

Matchups to watch: Saints C Erik McCoy vs. Giants DI Dexter Lawrence

Despite the Saints’ offensive line featuring three first-round picks, it’s the veteran Erik McCoy who continues to be the team’s most consistent blocker up front. McCoy has anchored the interior as a pass blocker, with his 78.8 PFF pass-blocking grade ranking second among all centers this season.

He will have his hands full this week against one of the game’s best interior defenders in Dexter Lawrence. While the former All-Pro has yet to record a sack this season, he maintains a solid 14.7% pass-rush win rate, granting him the seventh-highest PFF pass-rush grade (80.0) among defensive tackles.    

Additional News: 

• Giants owner John Mara diagnosed with cancer
• Giants WR Malik Nabers (knee) suffered season-ending injury; sparks renewed criticism of Metlife Stadium turf
• Saints TEs Taysom Hill (knee) & Foster Moreau (knee) expected to return to practice this week
• Saints G Cesar Ruiz (ankle) will miss Week 5, considered week-to-week
• Giants QB Jaxson Dart (hamstring) expected to be okay and practice this week
• Giants QB Russell Wilson expected to emerge as trade candidate

Storyline of the game: Cowboys look to break trends

Dallas’ start to the 2025 season has been a mixed bag, with strong performances as the underdog and some struggles as the favorite. The last time the Cowboys were road favorites in Week 3, they lost by 17 to the Bears in Chicago. However, coming off a good home performance against the Packers, Dallas will hope to ride renewed momentum into this contest.

Matchups to watch: Cowboys QB Dak Prescott vs. Jets pass rush

The Jets have had difficulties generating pressure — ranking 29th in pressure rate (28.4%) and 25th in PFF pass-rush grade (66.1). However, this week, they hold an advantage over a Cowboys offensive line that has struggled even more in pass protection, holding the lowest PFF pass-blocking grade (34.0) in the NFL. This could be the matchup in which the Jets find a boost.

At the same time, that slight disadvantage may not end up mattering, as Dak Prescott has been lethal under pressure this season. His 87.5 PFF passing grade under pressure leads the NFL, powered by a league-leading eight big-time throws to just three turnover-worthy plays.  

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Storyline of the game: Eagles DC Vic Fangio faces off with former team

During his time in Denver, Vic Fangio maintained top-eight defenses in PFF grading in two of his three seasons. It’s been three years since Fangio and the Broncos parted ways, and both still possess impressive strengths on the defensive side of the ball. Now, Fangio faces off against his former squad with hopes of staying undefeated and shutting down the Broncos’ offense. However, the Broncos won’t go down without a fight after posting a commanding victory in primetime that gives this team momentum heading into October.

Matchups to watch: Broncos WR Courtland Sutton vs. Eagles CB Quinyon Mitchell

While the Broncos’ offense has had some issues with consistency to start the year, one player that has been a staple of Denver’s success in the passing game is Courtland Sutton. Sutton has been dangerous down the field, having hauled in seven receptions of 15 or more yards — including three touchdowns, one in three out of his four games.

After an up-and-down start to the year, Quinyon Mitchell turned it on in Week 4 to post his highest PFF coverage grade (88.9) of the season. He locked down Bucs receivers, allowing just two catches on nine targets for just six yards while notching five forced incompletions. 

Additional News: 

• Questions of Eagles’ cohesion in question after social media post from WR A.J. Brown
• Eagles EDGE Ogbo Okoronkwo (tricep) will miss the remainder of the season
• Eagles LB Nakobe Dean (knee) has 21-day practice window opened

Storyline of the game: Titans’ struggles reach new low

Week 4 was a brutal performance from the Titans, being shut out on the road against their AFC South rivals in Houston. The frustrations have started to boil over, with first-year quarterback Cam Ward voicing frustration during the postgame press conference. The Titans’ offense has yet to build a foundation with Ward under center, as the team finished September as the lowest-graded offense (54.8) in the NFL.

Matchups to watch: Cardinals RB Michael Carter vs. Titans front seven

Although it’s not yet clear who will get the majority of the rushing workload for the Cardinals amid injuries to James Conner and Trey Benson, PFF’s Nathan Jahnke anticipates it will be Michael Carter to be the early-down back. Carter has seen limited run in recent years, but he maintained a solid 68.4 PFF rushing grade in his three-game stint at the end of last season.

There could be opportunity for Carter to find production against a Titans defense that ranks 28th in EPA per rush allowed. This past week against the Texans, Woody Marks and Nick Chubb were able to rack up 116 yards on the ground, with the rookie also finding the end zone. 

Additional News: 

• Titans RB Tyjae Spears (ankle) has practice window opened this week
• Titans QB Cam Ward frustrated with team’s performance to start the year
• Cardinals RB Trey Benson (knee) placed on IR

Storyline of the game: Sam Darnold & Baker Mayfield flourishing

In 2022, Baker Mayfield and Sam Darnold were teammates on a poor Panthers offense, an unfortunate situation where neither found much success. Fast forward to 2025, and both find themselves leading new franchises to tremendous heights, revitalizing their careers in new cities. Both Darnold (91.1 PFF grade; second) and Mayfield (72.6; 12th) hold top-12 grades at the quarterback position and lead a pair of playoff contenders in the NFC.

Matchups to watch: Buccaneers RB Rachaad White vs. Seahawks CB Devon Witherspoon

While this is an uncommon matchup to highlight, it will be one that is sure to appear in a crucial spot in blitz pickup. The Hawks frequently deploy Witherspoon on slot blitzes to catch offensive protection off guard, and he stands as one of the most effective blitzing cornerbacks in the NFL. While he has seen limited action this year due to injury, Witherspoon has recorded three pressures on four blitzes, including a clean-up half sack against the Cardinals this past week.

White will need to stay on his toes in blitz pickup, always keeping an eye on No. 21. Although his performance in pass protection has been a mixed bag early this season (54.9 grade), he held strong throughout last season, registering a 69.2 PFF pass-blocking grade. That’s an indication that White is capable of standing up to pressure. 

Additional News: 

• Teams monitoring Seahawks CB Riq Woolen as potential trade target
• Buccaneers RB coach Skip Peete recovering after suffering medical situation during practice Wednesday
• Buccaneers RB Bucky Irving (ankle) seen in walking boot at practice

Storyline of the game: Lions affirming elite status

After dropping Week 1 on the road to the Packers, the Lions rattled off three commanding victories. This past week, Detroit hung 34 on the highest-graded defense in the NFL in the Browns. The Lions covered as 10-point favorites at home and now face an even larger spread as road favorites in Cincinnati. 

Matchups to watch: Bengals RT Amarius Mims vs. Lions EDGE Aidan Hutchinson

Aidan Hutchinson’s return to the field has sparked this Lions defense early in the year. He picked up right where he left off prior to his injury last season, with his 92.3 overall PFF grade ranking second among all edge defenders. Through September, Hutchinson has already racked up 23 total pressures — including five sacks, tying for the NFL lead.

Mims will have his hands full with this matchup given his struggles in pass protection to start the year. The second-year tackle has produced a 49.3 PFF pass-blocking grade, ranking 54th out of 71 qualifying tackles. Against the Broncos on Monday night, he surrendered five total pressures, including a pair of sacks. That doesn’t bode well for his chances in this one.

Additional News: 

• Lions DI Alim McNeill (knee) will have 21-day practice window opened this week
• Lions CBs Terrion Arnold (shoulder) & D.J. Reed (hamstring) dealing with injuries; Reed expected to miss multiple games

Storyline of the game: Jayden Daniels set to return

After missing the last two games, Jayden Daniels is set to make his return to the lineup against a Chargers team looking to bounce back from an upset loss to the Giants in Week 4. While his presence will provide a morale boost to the Commanders, their difficulties to start the year haven’t stemmed from the signal caller. Marcus Mariota played well in Daniels absence, posting an 91.8 overall PFF grade.

Matchups to watch: Chargers pass protection vs. Commanders pass rush

The Chargers suffered yet another devastating loss up front, with Joe Alt expected to miss multiple weeks after being knocked out of their Week 4 matchup. Without Alt, Justin Herbert was under fire, with the Chargers allowing a 16.7% knockdown rate and recording a 27.5 PFF pass-blocking grade. 

While the Commanders don’t possess the same level of pass-rush talent as the Giants — who just teed off on Herbert — they are performing at a much higher level than 2024. Through the first month of the year, Washington ranks 14th PFF pass-rush grade (70.9) while also maintaining a top-10 mark in pressure rate (41.8%).

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Storyline of the game: Bills’ dominance meets surging Patriots

There’s little question regarding which team stands atop the AFC through the first month of the season. The Bills have put on a show, posting dominant wins and turning it on in close games when it matters most. Now, they face a division rival in the Patriots — who have been playing well as of recent, coming off their own commanding performance against the Panthers this past week. Attention now turns to whether or not the Pats can carry that momentum on the road against a contender like the Bills.   

Matchups to watch: Patriots RG Mike Onwenu vs. Bills DI DaQuan Jones

The Patriots’ overhauled offensive line has shown marked improvement protecting Drake Maye. As the lone holdover from last year’s unit, Mike Onwenu has matched the energy. His 79.7 PFF pass-blocking grade ranks third among qualifying guards. Onwenu has surrendered just a 3.8% pressure rate and earned above a 73.0 pass-blocking grade in each of his four starts. 

Similarly, Jones has been off to an excellent start rushing the passer to start the year. He’s tallied a pair of sacks on the year off a 14.1% pass-rush win rate. That play has culminated in a strong 80.7 PFF pass-rushing grade, the sixth-highest among interior defenders.   

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Storyline of the game: Building momentum in the AFC

Both the Chiefs and Jags closed out September playing inspired ball. After a rough 0-2 start to the year, Kansas City has marched through the Giants and Ravens in dominant fashion. Now, the Chiefs hope to ride that wave in Jacksonville, against a Jaguars team that is also building hype following a strong victory over the 49ers. Powered by an opportunistic defense with a knack for creating takeaways, the Jags will aim to prove their worth against a perennial powerhouse in the AFC.

Matchups to watch: Chiefs WR Xavier Worthy vs. Jaguars CB Jourdan Lewis

After missing the majority of the first three games of the year, Xavier Worthy’s return to the lineup infused new life into the Chiefs’ offense. The young receiver posted a 81.0 overall PFF grade against the Ravens, hauling in five of his eight targets for 83 yards and adding another two carries for 38 yards. His availability opens up numerous possibilities and big-play potential for this offense.

Jourdan Lewis has been an excellent addition to this Jaguars secondary. He owns the third-highest PFF coverage grade (83.5) at the cornerback position, while seeing snaps both in the slot and outside. This season, he’s allowed just 0.70 yards per coverage snap while holding passers to just a 39.7 passer rating on throws into his coverage.

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