Thursday Night Football Preview

NFL

Thursday, September 25, 2025 – 8:15 PM ET

SoFi Stadium

Los Angeles Rams vs San Francisco 49ers

The NFC West rivalry takes center stage on Thursday night as the San Francisco 49ers head to Los Angeles to battle the Rams. This game, with its unpredictable twists and turns, has all the intensity of a divisional matchup. Still, the numbers point to two strong betting angles: backing the 49ers to cover as sizable underdogs and fading Matthew Stafford to stay turnover-free.

Matchup Breakdown:

San Francisco enters the game with a twist of uncertainty at quarterback — Brock Purdy's absence has left the reins in the hands of Mac Jones. This unexpected shift in the offensive strategy adds an element of intrigue to the game. Despite this change, the 49ers maintain their balance through the versatile Christian McCaffrey, who has amassed an impressive 530 scrimmage yards and 2 TDs in four games. The short passing game and run-heavy approach, coupled with Jones's efficiency (66.3% completion rate, 4 TD, 1 INT), continue to be viable ways to control the tempo.

The Rams have heavily relied on Stafford’s arm early in 2025. His passing game, averaging 278.5 yards per game with 8 touchdowns and 2 interceptions through four contests, has been a key factor in their offensive strategy. His connection with Puka Nacua (503 yards) and Davante Adams (269 yards, 3 TDs) has kept the offense humming. However, Stafford faces a 49ers front that ranks top-10 in both sack rate and QB hits, which could disrupt his passing game.

Defensively, San Francisco has thrived in coverage, allowing just 5.4 yards per attempt with multiple players capable of creating turnovers (Kamren Curl and Cobie Durant each have interceptions). The Rams, meanwhile, rank near the bottom of the league in 3rd-down defense (48.1% allowed) and have been vulnerable in coverage, particularly against tight ends.

Betting Angles:

Even without Purdy, San Francisco has enough weapons to stay competitive. McCaffrey’s dual-threat role and a defense that excels at limiting explosive plays suggest this spread is inflated. Our projections give the 49ers a decent chance of covering +7.5, with the fair line closer to +5.

Stafford has thrown two interceptions in 4 games, but the matchup tilts against him. The 49ers’ disguised coverages, which involve the defense hiding their intended coverage until the last possible moment, and top-10 pressure rate create an environment where mistakes are likely to occur. He’s averaging a pick every 68 attempts. Given San Francisco’s ability to force QBs into bad decisions, the probability of at least one interception is higher than the plus-money market implies.

Conclusion:

This Thursday night clash sets up as a nail-biting, tight divisional battle. The 49ers’ defense is strong enough to disrupt Stafford. At the same time, McCaffrey and Jones should do enough offensively to keep the margin within a score. Both plays are individually strong, yet also closely correlated. If San Francisco covers, there’s a good chance Stafford has been forced into at least one turnover along the way.

Picks:

🎯 San Francisco 49ers +7.5 (-115)

🎯 Matthew Stafford over 0.5 Interceptions (+104)