Week 15 is nearly a wrap, and betting lines are now available for Week 16. Here are our favorite early spread picks for the slate.
San Francisco 49ers (-4.5) vs. Indianapolis Colts [Total: 45.5]
Best Bet: Over 45.5
Points have been at a premium for the Colts amid uncertainty at quarterback, although they've also faced strong defenses over the past three games, all ranking in the top five in EPA allowed per play. That won’t be the case against the 49ers, whose defense ranks 31st in positive EPA rate (48.6%) since the start of November.
A 44-year-old Philip Rivers isn’t going to rip throws like he did before retirement, but the Colts' offense can get back on track behind Jonathan Taylor and the run game. The 49ers’ missed tackle percentage against the run has risen over the past three games to 18% — the fifth-highest rate in the league — resulting in an NFL-high 3.6 yards after contact per attempt allowed. As the only back in the NFL with more than 1,000 yards after contact this season, Taylor can break this game open.
For the 49ers, the matchup advantage lies with Brock Purdy and the passing game. Against the Titans, San Francisco generated the fourth-highest EPA per dropback of Week 15, helping the offense score on seven of their eight drives.
The Colts’ coverage unit has been a pain point all year. Since returning from their bye in Week 11, they rank 25th in PFF coverage grade (49.3) and EPA per dropback. Plus, star cornerback Sauce Gardner’s health and status are still uncertain after he missed his second straight game.
The NEW PFF Player Props Tool
Weekly prop plays, predictive models and matchup edges for the 2025 season.
Explore Top Player PropsLos Angeles Rams (-1.5) vs. Seattle Seahawks [Total: 44.5]
Best Bet: Seahawks ML (+105)
The Seahawks are coming off a slightly disappointing outing in which they needed a game-winning field goal to eke out a win against a Colts team starting 44-year-old quarterback Philip Rivers and in which they were 13-point favorites.
But the final score was perhaps slightly misleading. The Seahawks outgained the Colts by nearly 100 yards and held Rivers to 120 yards on 27 attempts while keeping running back Jonathan Taylor to 3.5 yards per carry on 25 rushes. Seattle went just 2-for-13 on third downs and could not convert drives into touchdowns, with their 18 points all coming from field goals.
The Rams, meanwhile, are a dominant team that carved up the Lions‘ defense in Week 15. But they did lose wide receiver Davante Adams to injury, and Puka Nacua exited the game, as well. This matchup with the Seahawks, without their main weapons, could present a bigger challenge than their typical opponent.
Rams quarterback Matthew Stafford has some of the most drastic splits when facing disruption or not, ranking as the NFL's best with no disruption but well below average when disturbed. The Seahawks' defense leads the NFL in disruption.