49ers vs Rams Predictions, Picks & Best Bets for Thursday Night Football Tonight

Osborne's prediction: Matthew Stafford and the potent Rams pass attack will pull away from their NFC West rivals.

Joe Osborne: Senior Betting Analyst at Covers
Joe Osborne • Senior Betting Analyst
Oct 2, 2025 • 17:21 ET • 4 min read

NFL

Match starts: 2 hrs
LA
61 %
SF
39 %
Read Analysis
San Francisco 49ers quarterback Mac Jones and Los Angeles Rams QB Matthew Stafford headline tonight's action at SoFi Stadium.
Photo By - Imagn Images. San Francisco 49ers quarterback Mac Jones and Los Angeles Rams QB Matthew Stafford headline tonight's action at SoFi Stadium.

Week 5 of Thursday Night Football pits two 3-1 teams against each other, with the Los Angeles Rams favored by 8.5 points over the San Francisco 49ers.

While the Rams appear poised for a deep playoff run, the 49ers are simply trying to stay afloat after a brutal first month plagued by injuries.

My 49ers vs. Rams predictions believe this is San Francisco’s biggest test to date. Along with the adversity of traveling on a short week without key players, my NFL picks break down why the Niners will have trouble staying competitive on October 2.

Kickoff is set for 8:15 p.m. ET from SoFi Stadium in Inglewood, with the game airing on Prime Video.

49ers vs Rams prediction

49ers vs Rams Best bet: Rams -8.5 (-110)

Coming into the season, much was made of the San Francisco 49ers' easy schedule. They’ve been able to take full advantage so far, but they’ve hardly been impressive.

We saw them squeak by the Seahawks, Saints, and Cardinals in their opening three games, then lose as a home favorite against the Jaguars in a game where they were down by 12 points with less than five minutes left on the clock.

Now the level of competition will rise significantly against a Los Angeles Rams team that typically doesn’t play down to the competition. Los Angeles is on a run that’s seen them go 11-4 ATS in their last 15 games as a favorite, with just one outright loss in this span.

I think this game sets up very nicely for Matthew Stafford and a Rams pass attack that ranks fifth in yards per pass attempt.

Stafford should have a lot of time to work as the 49ers are struggling to disrupt opposing QBs. They come in ranked 29th in pressure rate and have just five sacks.

San Francisco also comes in at 25th in opponent completion percentage, and they’ve yet to face a passing game of the caliber of the Rams.

While the 49ers’ defense will likely have its hands full, I think the offense will have trouble keeping up.

To make matters even more challenging for the 49ers, Mac Jones will step in for Brock Purdy, and he'll be working with a skeleton crew of wide receivers, with both Ricky Pearsall and Jauan Jennings set to miss the game.

While Christian McCaffrey has looked good this season, this 49ers offense isn’t even remotely close to where they were in 2023 when this era of the team was at its peak. That’ll happen when you remove George Kittle and prime versions of Deebo Samuel and Brandon Aiyuk from a lineup.

Let’s not forget an injury-ravaged 49ers team went 1-7 to close out 2024, and it looks like history could repeat itself in 2025. 

49ers vs Rams TNF same-game parlay

The path to winning and covering will come through the air for the Rams.

Stafford should have plenty of time to work against this light pass rush of the 49ers, who've yet to play a top-tier offense this season. Stafford will have the ability to pick apart a defense that ranks 25th in opponent completion percentage.

Expect Davante Adams, who's had 50+ yards in every game this season while ranking tied for the league lead in red-zone targets, to benefit.

49ers vs Rams 4-leg SGP

  • Rams moneyline
  • Matthew Stafford Over 234.5 passing yards
  • Davante Adams Over 53.5 receiving yards
  • Davante Adams anytime touchdown

Our big-ticket SGP: Jones adds to Niners' woes

I expect the 49ers to be playing from behind, which will force Jones to throw more and potentially make a mistake.

49ers vs Rams 5-leg SGP

  • Rams moneyline
  • Matthew Stafford Over 234.5 passing yards
  • Davante Adams Over 53.5 receiving yards
  • Davante Adams anytime touchdown
  • Mac Jones Over 0.5 interceptions

49ers vs Rams game predictions

49ers vs Rams moneyline prediction

The Rams don't play down to the competition, as they have wins in 14 of their last 15 games as a favorite.

I expect them to take full advantage of this watered-down version of the 49ers.

49ers vs Rams spread prediction

San Francisco tends to get by on reputation based on success from previous seasons and having respectable coaching, but this beat-up version of the team is probably a Bottom-10 team in the NFL.

Don't be surprised if L.A. lays the smack down on their division rival and wins by 10+ points.

49ers vs Rams Over/Under prediction

This could be a classic TNF snoozer that goes Under.

Both defenses are among the best at limiting yards per play and third-down conversions, while each offense is struggling in the red zone — especially San Francisco, which ranks 27th in RZ TD conversion percentage.

49ers vs Rams odds

  • Spread: San Francisco +8.5 (-110) | Los Angeles -8.5 (-110)
  • Moneyline: San Francisco +350 | Los Angeles -450
  • Over/Under: Over 44.5 (-110) | Under 44.5 (-110)

49ers vs Rams betting trend to know

Los Angeles has covered the 2Q Spread in 15 of its last 19 games (+10.60 Units / 48% ROI). Find more NFL betting trends for 49ers vs. Rams.

How to watch 49ers vs Rams

Location SoFi Stadium, Inglewood, CA
Date Thursday, October 2, 2025
Kickoff 8:15 p.m. ET
TV Amazon Prime

Learn how to live stream 49ers vs. Rams for free.


More Thursday Night Football picks and odds from Covers


49ers vs Rams latest injuries

Brock Purdy has been ruled out for tonight’s game against the Rams due to turf toe.

The 49ers announced that Mac Jones will start in Purdy’s place, with multiple media outlets reporting the decision on Thursday morning. There's no doubt the Niners will miss Purdy's elite processing speed in Shanahan’s full-field, motion-heavy play-action game.

So, how will things look tonight with Jones? Bettors should expect a tighter, more risk-averse script with heavier early down runs and screens through Christian McCaffrey, more quick-game from shotgun, mirrored half-field reads, and fewer deep-over/play-action shot sequences. 

Protection will be prioritized with more six- and seven-man looks and defined launch points to keep Jones clean. The net effect is lower explosive-play volatility but steadier drive sustainability. Defenses may squeeze the box and squat on underneath windows unless Jones proves he can hit outside the numbers.

49ers vs Rams weather

Expect classic SoCal football weather in Inglewood tonight: dry and mild, with temperatures easing from the low 70s around kickoff into the mid-to-upper 60s by the second half. Skies trend mostly clear to partly cloudy, and rain isn’t in the picture.

In short, pleasant conditions outside (and even more so under SoFi’s translucent roof).

On-field impact should be subtle. With no meaningful precipitation and typically light evening breezes, quarterbacks can spin it and kickers should get near-“indoor” reliability; the ball should carry normally, and footing on the fast turf will favor sharp cuts and timing routes.

If a shallow marine layer sneaks in late, it could add a touch of moisture to the ball and make returns/ball security marginally trickier, but overall, the weather gives neither the 49ers nor Rams a distinct edge.

Monitor gametime conditions with our live NFL weather info and learn how weather impacts NFL betting.

Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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Joe Osborne Senior Betting Analyst Covers.com
Senior Betting Analyst

Joe is an industry veteran who loves the entertainment aspect of the sports betting industry. His opinions are always backed by data and he enjoys digging into the numbers and coming up with interesting nuggets to share with sports bettors.

Joe takes a high-energy and fun approach to covering his favorite sports which include the NFL, MLB, UFC, NBA and NHL, and there’s no bet type he loves more than an NFL six-point teaser. Joe is the host of our daily sports betting program, Before You Bet, while he also leads our weekly UFC show, P4P Picks, and our 'Covers on the Ground' series where he's covered many UFC, NFL and NBA games in person. A monthly highlight for Joe is conducting interviews with UFC legend Georges St-Pierre ahead of every UFC PPV.

Outside of his work at Covers, Joe has appeared on many top media brands including ESPN Radio, Mad Dog Sports Radio, VSIN, TSN, and SportsNet. He always recommends not reading too much into narratives when placing your bets as those factors are already cooked into the lines set by oddsmakers.

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