Week 5 kicks off with an excellent game on Thursday Night Football between the San Francisco 49ers (3-1) and the Los Angeles Rams (3-1). Here are the odds, prediction, and free expert picks for 49ers vs. Rams.
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49ers vs. Rams: Game Information
Primetime in LA.
🎟️: https://t.co/6r14urC6dR pic.twitter.com/ijjjKNx02C
— Los Angeles Rams (@RamsNFL) September 30, 2025
- 🏈 Game: Seahawks vs. Cardinals
- 🗓️ Date: Oct. 2
- 🕗 Time: 8:15 p.m. ET
- 🏟 Location: SoFi Stadium — Inglewood, California
- 💻 Live Stream: Prime Video, NFL+
49ers vs. Rams Odds and Predictions
3rd most in the League 👏 pic.twitter.com/UYjGrz2cSR
— San Francisco 49ers (@49ers) September 30, 2025
The 49ers continue to be the walking wounded.
49ers quarterback Brock Purdy returned in Week 4’s 26-21 loss to the Jacksonville Jaguars. Purdy finished 22 of 38 for 309 yards, two touchdowns, and two interceptions.
However, Purdy reaggravated his toe injury that kept him out of Weeks 2 and 3. After Purdy was a non-participant at practice on Monday, 49ers general manager John Lynch said the quarterback is questionable for Thursday night’s game.
The 49ers will be without Nick Bosa, George Kittle, and Brandon Aiyuk because of injuries. Wide receivers Ricky Pearsall and Jauan Jennings are questionable for Thursday night.
The 49ers can’t catch a break in terms of staying healthy.
On a short week, the 49ers must travel to Los Angeles to play a Rams team that handed the Colts their first loss on Sunday. Matthew Stafford completed 29 of 41 passes for 375 yards and three touchdowns in the 27-20 victory.
Puka Nacua is off to an insane start thanks to his league-leading 42 receptions and 503 yards. Nacua looks like 2021 Cooper Kupp, who won the wide receiver triple crown and Super Bowl MVP.
If Purdy does play and the 49ers remain an underdog, that’s not a good sign. San Francisco is 0-3 SU and ATS when Purdy’s an underdog.
The line reflects Purdy’s injury and suggests that backup quarterback Mac Jones will play instead. Jones is also dealing with a knee injury, and if he can’t go, Adrian Martinez would likely get the start.
If Purdy is ruled out, expect this line to move to 7. While I would still like the Rams in that situation, getting it at 5.5 is a huge advantage. I expect Sean McVay and the Rams to take care of business at home on a short week.
Pick: Rams -5.5 (-120)
49ers vs. Rams Prop
Christian McCaffrey has been the 49ers’ best player on offense this season. McCaffrey has over 525 yards of total offense, including 305 receiving yards.
Even if Purdy can play, his mobility could be limited, meaning McCaffrey will be the primary option on the ground.
The Rams have a stout run defense (98.5 yards per game). However, teams have tried to establish the run on the Rams all season. The lead running back for the Rams’ opponents in the last three games has at least registered 17 carries.
I expect McCaffrey to do the same, who has 17 or more carries in three of four games this season.
