NFL · 2 hours ago

NFL Thursday Night Football Best Bets: 49ers vs Rams

Gabriel Santiago

Host · Writer

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NFL season (and all its spoils) is in full throttle. Summer is gone, fall is here, and incidentally, there are betting opportunities nearly every day between now and next February. We’ve got you covered for Week 5, which kicks off with a divisional showdown on Thursday Night Football!

Where to Watch San Francisco 49ers vs. Los Angeles Rams

Stadium: SoFi Stadium
Location: Inglewood, CA
Where to Watch: Prime Video
Time: 8:15 p.m. ET
Spread: LAR -7 (-115) | Total: 45.5 (-106/-114)
Moneyline: SF +295 | LAR -370

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The Los Angeles Rams (3-1) will start the football week by hosting a shuffling version of the San Francisco 49ers (3-1). Entering 2025, the injury concern around Matthew Stafford was prevalent, but he has dazzled through all four games. Meanwhile, 49ers signal-caller Brock Purdy is out for Thursday; this will be Purdy’s third missed contest of the short season.

This primetime affair between Los Angeles and San Francisco will declare first place within the NFC West for the time being. These divisional foes have both won multiple gritty games in 2025, but again, the Niners are arriving in Southern California mostly depleted. Along with Purdy, starting wide receivers Jauan Jennings (ankle), Ricky Pearsall (knee), and tight end George Kittle (hamstring) will also be missing from action at SoFi Stadium. With that, prepare to see Mac Jones taking the snaps along with an active Christian McCaffrey.

The Rams are rolling right now. Stafford is still playing high-quality football in Year 17, completing passes at a 67.6% clip. He has developed a deep love for throwing the football to Los Angeles receiver Puka Nacua. After just four weeks, Nacua has already notched 42 receptions for 503 yards, on pace to set NFL records in both categories.

Given the many injuries for San Francisco, it is tough to see them taking down this fully healthy Rams team. Additionally, the 49ers have not covered the spread as an underdog since 2022. That amounts to five consecutive ATS losses when they are not favored. Incidentally, I am willing to lay the seven points on Los Angeles at home.

Best Bet: Rams -7 (-105)

With a combined total of 45.5 points in this bid, my initial lean is towards the under.

Not only does San Francisco’s offense have several question marks this week, but the 49ers are still playing high-end defense (even without former DPOY Nick Bosa). To this point, S.F. has allowed only 18.8 PPG, which is a top-seven figure. In terms of total yardage allowed (280.5 YPG), this group from Northern California is tied for fifth in the NFL.

Notably, Los Angeles has myriad offensive weapons. Aside from Nacua, Davante Adams and Tyler Higbee are both great options in the passing game. However, they will be dealing with the heat of 49ers linebacker Fred Warner, one of the rangiest players in the game.

The Rams are anything but one-sided in the current campaign. When I review Los Angeles’ defensive figures in 2025 (20.3 PPG/284.5 YPG), my faith in under 45.5 total points here is solidified.