Week 5 of the 2025 NFL season kicks off Thursday as the calendar officially moves into October with the Los Angeles Rams hosting the San Francisco 49ers. The Rams are coming off a big win over the Colts, while the 49ers were unable to top the Jaguars as they continue to battle injuries. Does San Francisco’s mounting health concerns make Los Angeles a good spread pick for Week 5?
Here’s a look at my five best spread picks for Week 5. My record is 7-8 through three weeks of making NFL spread picks, incorrectly taking the Chargers and Bucs a week ago but correctly predicting the Lions and Bears would cover.
Best spread picks for NFL Week 5Texans -1.5 vs. Ravens
Houston hasn’t been great to start this season, but the Texans did dominate the Titans a week ago and have remained stellar defensively. They should be able to handle a Baltimore side that is not only missing Lamar Jackson but also has a long list of injuries on the defensive side of the ball. Cooper Rush has proven to be an effective backup in spot duty, though I think Houston’s defense will gladly take facing him over Jackson any day. It’s likely to be an ugly game, but I’ll take the Texans in what is essentially a pick ’em. The SportsLine Inside the Lines team model likes Baltimore +1.5, as the Ravens cover in 54% of simulations.
Eagles -3.5 vs. Broncos
Philadelphia didn’t complete a single pass in the second half of its Week 4 win over the Bucs, leading to frustration from star receiver A.J. Brown and more questions about the Eagles’ ability to generate points consistently. The Broncos are coming off a dominant win on Monday over the Bengals, getting a 100-yard game from a running back for the first time since Week 18 of the 2022 season. That being said, Philadelphia has managed to show up when it absolutely needs to. Jalen Hurts has been making plays routinely with his arm and legs, which should be enough to cover this tight spread against Denver. The SportsLine model has the Eagles covering in 58% of simulations, good for an “A” grade.
Colts -7 vs. Raiders
Betting whole numbers can be frustrating, so I’d take this down to Colts -6.5 at most sportsbooks. Indianapolis is clearly better than expected, and Daniel Jones is no fluke. He’s got total command of this offense, and the defense has been solid despite some roster shuffling. The Raiders have been abysmal to start the season, and even with Ashton Jeanty coming off a breakout game in Week 4, I don’t see Pete Carroll’s squad doing much on the road in Week 5. The Colts cover in 55% of SportsLine model simulations.
Lions -10.5 vs. Bengals
Things have been surprisingly rough for the Bengals. Joe Burrow being out was always going to hurt the team, but Jake Browning showed he was capable in 2023, and that’s why Cincinnati signed him to an extension. Browning has failed to move the ball in his last two starts, and there’s frustration with star receivers Ja’Marr Chase and Tee Higgins not performing. The Lions, meanwhile, are humming offensively and have no problem running up the score on bad opponents. Detroit covers at home in 54% of model simulations.
Bills -7.5 vs. Patriots
There’s a lot of buzz in New England after the Patriots demolished a bad Panthers team in Week 4. However, this team does not have nearly enough firepower to take down a red-hot Buffalo squad in Orchard Park. The Bills have had some minor scares at times early in this season, but they’re 4-0 and should have no problem grinding down this Patriots team. Buffalo covers in 70% of SportsLine model simulations, good for an “A” grade.