Analyzing the Standout Matchups in Week 5

There are a lot of factors to consider before making NFL picks for Week 5. Injury reports are getting increasingly cluttered and there’s the tricky task of figuring out which trends to take seriously from the first four weeks of the campaign.

This week’s slate isn’t quite as tantalizing as Week 4, but we’ve still got six intriguing games to analyze.

Philadelphia Eagles @ Jacksonville Jaguars, Sunday 9:30 a.m. ET

Game Context

The 2-2 Eagles are looking to get back on track after consecutive losses, including a blown lead at the hands of the Rams. Philadelphia will do so with an overhauled offensive line and no Saquon Barkley and possibly without DeVonta Smith.

The Jags are the nominal home team in London after back-to-back impressive wins. Jacksonville is tied for the second-best offense by EPA per play, and their defense ranks in the top 10.

What To Look Out For

Will Shipley looks like he’ll be Philly’s lead back. Jacksonville has been an elite run defense this year, and they’ve generated plenty of pressure without having to blitz. We’ve not seen many heavy boxes.

It’s been alarming how poor this Eagles defense has been in all facets. They need to be able to stop the Jags on the ground or Trevor Lawrence will boss this game.

Key Questions

· Can Philly run the ball?

· How do the Eagles cope against multiple tight-end looks?

Minnesota Vikings @ New Orleans Saints, Sunday 1 p.m. ET

Game Context

By some sort of football miracle, the Vikings are 4-0. The defense is elite, but the offense has mustered only 47 points over the last three games against favorable opponents.

The 1-3 Saints could have easily gone 3-0. A loss to the Raiders was followed by a shambolic performance against Atlanta. New Orleans couldn’t protect Tyler Shough, couldn’t run the ball, and was torched by the Falcons’ running backs.

What To Look Out For

Not many teams put two running backs on the field as often as the Vikings. New Orleans has the worst run defense by EPA per play in the NFL. Look for Minnesota to lean heavily on Aaron Jones once again.

Brian Flores loves blitzing with these Vikings, contributing to the highest pressure rate in the NFL. New Orleans struggled to keep Shough upright on Monday.

Key Questions

· Can the Saints give Shough time in the pocket?

· Will the Vikings scrape together enough offense through Jones?

Las Vegas Raiders @ New England Patriots, Sunday 1 p.m. ET

Game Context

The Raiders might have lost to the Chiefs in Week 4 to fall to 3-1, but the performance showed they are for real. New England kickstarted its season with an impressive road win in Buffalo, which included a return to 2025 form for Drake Maye.

It will take back-to-back performances for bettors to rebuild confidence in Maye. Vegas’ defense is a challenge for the Patriots’ quarterback.

What To Look Out For

The Raiders have been great at defending the pass. Much of that is down to how easily they are pressuring opposing quarterbacks without needing to send extra bodies. That’s going to be a test for Maye – will his decision-making hold up under pressure?

We’re going to see a lot of 12 personnel from Vegas with their dynamic tight end duo. It’ll be interesting to see how the Patriots try to cover Brock Bowers and Michael Mayer.

Key Questions

· Can Maye repeat his Week 4 showing?

· Do the Patriots have the protection to slow down Vegas’ pass rush?

San Francisco 49ers @ Seattle Seahawks, Sunday 4:25 p.m. ET

Game Context

The 4-0 49ers take on the 3-1 defending champion Seahawks. Seattle has been as expected on defense, but the offense has been up and down, despite scoring 30+ points in each of the last three games.

San Francisco has been battling injuries all year. It just doesn’t seem to impact Kyle Shanahan’s team from racking up wins. A 10-point win over Denver was a real statement from the Niners, who have taken advantage of a favorable schedule to produce far and away the league’s best offense.

What To Look Out For

Brock Purdy has been lights out so far, throwing only one pick to 11 touchdowns. He’s yet to take a sack. Sam Darnold missed time through injury and has a 4.3% interception rate.

Keep a close eye on the injury report. Mike Evans, Christian McCaffrey, Trent Williams, Kyle Juszczyk, Dre Greenlaw, and Nick Bosa all feature for the Niners at the time of writing.

Key Questions

· Does Darnold live up to Purdy’s All-Pro level?

· How many of San Francisco’s injury concerns are active?

Baltimore Ravens @ Atlanta Falcons, Sunday 8:20 p.m. ET

Game Context

Atlanta has gone 2-0 with Michael Penix Jr. under center with two explosive offensive performances. Baltimore is dealing with uncertainty over Lamar Jackson’s availability as they try to move to 4-1.

These are two dynamic rushing attacks led by Bijan Robinson and Derrick Henry. The Falcons defense was rock-solid against the run on Monday night, but stopping Henry and potentially Jackson is a much bigger ask.

What To Look Out For

Atlanta is a stout run defense. They don’t allow explosive plays and they stuff plenty. When the quarterback drops back to pass, the Falcons are dangerous too, with a high contested target rate and a high pressure rate.

Both teams like running multiple tight-end looks and running the ball. It’s going to be a bruising game in the trenches.

Key Questions

· Who wins the turnover battle?

· Does Baltimore have enough if Jackson isn’t 100%?

Buffalo Bills @ Los Angeles Rams, Monday 8:15 p.m. ET

Game Context

It doesn’t get much more heavyweight than this. The Rams, the preseason Super Bowl favorites, are 2-2 after a come-from-behind win over the Eagles in Week 4. Buffalo dropped to 3-1 with a disappointing loss to the Patriots.

This is a matchup of the last two league MVPs and it’s rightly given a primetime slot.

What To Look Out For

Both teams are facing injury concerns over their lead receivers in Puka Nacua and D.J. Moore. For Buffalo, all eyes are on Keon Coleman to see if he can build on a breakout performance. The Rams used Kyren Williams a lot as a receiver to supplement Davante Adams.

Los Angeles isn’t afraid of going with a light box, but do they dare do that against Josh Allen and James Cook? The Rams haven’t been great against the run, which only opens up more play-action opportunities for Buffalo.

Key Questions

· Has Coleman turned a corner?

· Does Bills' secondary keep Nacua/Adams quiet?