49ers vs. Rams Final Score Prediction for NFL Week 5 (L.A. Heavily Favored at Home)

The Rams are favored at home on Thursday.

The Los Angeles Rams are 91-58 at home under head coach Sean McVay. / Eric Hartline-Imagn Images

Thursday Night Football in Week 5 features a huge NFC West battle between the 3-1 Los Angeles Rams and the 3-1 San Francisco 49ers.

Three teams in the NFC West (L.A., San Fran and Seattle) are 3-1 through four weeks, and a win for either team on Thursday could put them in the driver’s seat to win this division.

Oddsmakers have set the Rams as favorites at home in this matchup, and this line has shifted towards L.A. with Brock Purdy, Ricky Pearsall and others out for San Francisco.

L.A.’s only loss this season came in the final seconds against an undefeated Philadelphia Eagles team, and Matthew Stafford has looked great despite dealing with a back injury before the 2025 season.

This season, the SI Betting team is attempting to predict the final score of every NFL game as a fun way to help bettors decide on their spread and total bets.

Using the latest odds and analysis for this matchup, here’s my prediction for this NFC West showdown on Thursday.

49ers vs. Rams Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• 49ers +6.5 (-112)
• Rams -6.5 (-108)

Moneyline

• 49ers: +240
• Rams: -298

Total

• 46.5 (Over -112/Under -108)

The odds for this game have moved a ton, as the Rams opened as three-point favorites on Sunday, but all of the 49ers’ injuries have shot this line up to Rams -6.5. 

Brock Purdy (turf toe) wlll not play on a short week, and that’s led to oddsmakers shifting this spread by 3.5 points. 

49ers vs. Rams Final Score Prediction

Earlier this week, I shared in SI’s betting preview for this game why I believe the UNDER is the best bet on Thursday night: 

These teams are two of the better defenses in the NFL, as they entered Week 4 at No. 4 (San Francisco) and No. 8 (Los Angeles) in EPA/Play on defense.

Now, they have a total that is nearing 50 in this Thursday night matchup, but I’m not sold on an offensive explosion in a short week.

So far this season, these teams are both 2-2 to the UNDER, and Thursday Night Football games have gone UNDER this number three times, finishing with 44, 45, 52 and 43 combined points.

Both of these teams would love to establish the run early, and while the Rams put up 27 points in Week 4, they benefitted from a few broken plays by the Colts secondary. 

On a short week, I wouldn’t be shocked to see this game go under, especially since Purdy has been at less than 100 percent to open this season.

I still believe that the UNDER is a strong play given all the injuries on the San Francisco side, but I also like the Rams to win.

Los Angeles is 91-58 straight up at home since Sean McVay took over as the team’s head coach, and it covered the spread in both of its games as a home favorite so far this season.

On a short week, I trust a healthy Rams team much more than this banged up San Francisco one that is coming off a loss to Jacksonville.

Final Score Prediction: Rams 23, 49ers 17

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Odds refresh periodically and are subject to change.

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