San Francisco 49ers vs Los Angeles Rams Prediction, Picks & Closing Odds

• The Rams are 8.5-point favorites over the 49ers tonight on TNF
• Brock Purdy, Ricky Pearsall, Jauan Jennings and George Kittle are out for San Francisco
• See below for my 49ers vs Rams picks and predictions, plus the SF vs LAR closing lines

Tonight’s San Francisco 49ers (3-1, 2-0 away) vs Los Angeles Rams (3-1, 2-0 home) NFC West showdown on Thursday Night Football was supposed to be a clash of top NFC contenders. Instead, it’s shaping up to be a lopsided affair.

That’s because San Francisco has been decimated by injuries on offense. As a result, online sportsbooks have listed LA as the heavy chalk in the latest TNF odds, going from -3.5 to -8.5 ahead of game time.

Kickoff is scheduled for 8:15pm ET from SoFi Stadium, in Los Angeles, CA, with Prime Video providing the broadcast coverage.

San Francisco 49ers vs LA Rams Prediction & Pick

• Under 44.5 (-125 at DraftKings)

If the Niners are going to be a factor in the Super Bowl odds, they’ll need to get healthy quick. Brock Purdy (toe) will miss his third game of the season tonight, but that’s just the start of the San Fran injury woes.

The 49ers will also be without their top-two receivers Ricky Pearsall (knee) and Jauan Jennings (ribs, ankle). They’re already down star tight end George Kittle (hamstring) and their most talented wideout Brandon Aiyuk (knee).

With Purdy out, Mac Jones will start his third game in 2025 after leading the team to wins over the Saints and Cardinals. San Fran’s offense wasn’t exactly a world beater in those two outings, averaging just 20 points per game. The assignment tonight is significantly more difficult, as LA boasts one of the better defenses in the NFC.

The Rams defense is second in the league in sacks, fifth in expected points added and ninth in yards allowed. They’ve allowed 20 points or less to three of four opponents, and were well on their way to keeping Philly below that number as well before a fourth quarter collapse. Jared Verse and Co. are excellent at generating pressure, which is problematic for Jones.

LA Rams Defensive Stats

The former 1st round pick is completing 71% of his throws from a clean pocket, but that number dips to 47% under duress. Jones has always struggled under pressure, posting 13 turnover worthy plays vs just 3 big time throws in 2023, the last time he saw significant playing time.

Scoring is going to be tough to come by for Niners tonight, which is why I lean under 44.5 points as my 49ers vs Rams prediction. On the other side of the ball, LA’s offense is quite potent, but I don’t expect them to have to show too much as significant favorites.

They should be content to bleed the clock with the running game, wearing down the San Fran defense in the process. The Niners are much healthier on that side of the ball, and enter play ranked seventh in scoring defense. They’ve held three of four opponents to 21 points or less, and are sixth in yards allowed per play.

With game script in the Rams favor, I expect we’ll see less volume for Puca Nacua. He currently leads the NFL in receiving yards and receptions, but LA shouldn’t have to have to force feed him like in previous weeks when they’ve been in tight games. For that reason, consider a fade of Nacua in the NFL player props market where his receptions over/under currently sits at 8.5.

Looking for more 49ers vs Rams plays? Check out the following:

• 49ers vs Rams same-game parlay
• 49ers vs Rams player prop bets

49ers vs Rams Betting Trends

As for the betting trends, San Fran has typically held the advantage over LA in the Kyle Shanahan-Sean McVay era, but lately that’s swung back in the Rams favor. They’ve covered in four straight meetings dating back to 2023.

49ers vs Rams Closing Odds

The best odds we can get on under 44.5 is -125 at DraftKings. If you like the over, visit BetMGM as they’re hanging a 43.5 at the moment. Spread wise, you can get +8.5 on the Niners at -105 at Bet365, while FanDuel is offering -8.5 at -105 odds on LA if you want to back the Rams.

Odds as of 5:15 pm ET, Oct. 2 New customers can claim the bet365 promo code and get a bonus to bet on 49ers vs Rams.

Per the NFL public betting percentages, the spread opened at LA -3.5 prior to the injury news, but has steadily moved towards the Rams all week. Interestingly enough, the total has fallen only 2 points since its opener, which I don’t believe is enough of a drop given the Niners poor health.