An NFC West clash takes place on ‘Thursday Night Football’ for the second week in a row with the Los Angeles Rams hosting the San Francisco 49ers to kick off Week 5. These teams are both 3-1, tying them atop the division alongside Seattle, which defeated Arizona on TNF in Week 4. San Francisco was handed its first loss of the year by the Jacksonville Jaguars on Sunday, falling 26-21 at home. Meanwhile, the Rams just handed the Indianapolis Colts their first defeat with a 27-20 victory in Week 4. Brock Purdy (toe), Jauan Jennings (ankle, ribs) and Ricky Pearsall (knee) have all been ruled out for San Francisco, while George Kittle (hamstring) remains on IR.
Kickoff is at 8:15 p.m. ET from SoFi Stadium in Inglewood, Calif. The Rams have won each of the last three meetings between the teams. The latest 49ers vs. Rams odds have Los Angeles as the 8.5-point favorite. The over/under for total points is 43.5, after opening at 47.5. L.A. is a -465 favorite on the money line (risk $465 to win $100), with San Fran at +358 (risk $100 to win $358). Before making any Rams vs. 49ers picks, be sure to see what the SportsLine projection model has to say.
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Now, the model has zeroed in on San Francisco vs. Los Angeles. You can head to SportsLine now to see its picks. Here are several NFL odds and betting lines for Rams vs. 49ers:
| 49ers vs. Rams spread | Los Angeles -8.5 at DraftKings Sportsbook |
| 49ers vs. Rams over/under | 43.5 points |
| 49ers vs. Rams money line | Los Angeles -465, San Francisco +358 |
| 49ers vs. Rams picks | See picks at SportsLine |
| 49ers vs. Rams streaming | Amazon Prime |
Why the 49ers can cover
Christian McCaffrey has clearly put last year’s injury-plagued season behind him as he’s been a workhorse this year, leading the NFL with 100 touches. His 530 scrimmage yards rank third in the league, and he’s feasted off the Rams over the course of his career. He’s had at least 135 scrimmage yards in all four games against Los Angeles, with five total touchdowns, and he’s averaged 105 rushing yards alone versus L.A. since he joined the 49ers.
The Niners defense has gotten back on track after a poor 2024 as it sits inside the top 10 in the major categories of points allowed, yards allowed, third-down defense and redzone defense. No team has had more than 186 passing yards against the 49ers, while they’re limiting the run game to under 4.0 yards per carry. Also, playing in Los Angeles hasn’t been much of a home-field advantage for the Rams in recent matchups as the Niners have won five of the last six regular season meetings between these two in L.A. See which team to back at SportsLine.
Why the Rams can cover
At 37 years old, Matthew Stafford is playing the best football of his career, with a 19:3 TD:INT over his last 11 games. That ratio could improve considerably after Thursday, considering the Niners’ struggles in picking off quarterbacks. San Francisco has gone 11 straight games without a defensive interception, which is tied for the longest streak by any team over the last 85 years. A lack of pass rush, this season, is playing a part in that, especially since Nick Bosa (knee) was lost for the year. Last week, San Fran generated pressure on just 16% of opponent dropbacks, which was the team’s fifth-lowest rate in a game since Kyle Shanahan became coach in 2017.
The Rams are 8-2 against the spread over their last 10 games, and no NFL team has a better spread record over this stretch. Additionally, Sean McVay always gets his teams ready for divisional battles as the Rams are 10-3-1 ATS over their last 14 games versus fellow NFC West opponents. Meanwhile, the Niners have lost four straight ATS as an underdog and are 2-6 versus the line in divisional games since the start of last year. See which team to back at SportsLine.
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How to make Rams vs. 49ers picks
For the NFL Week 5 Thursday Night Football game of 49ers vs. Rams, the model is leaning Over the total, projecting 46 total points. It also says one side of the spread hits over 50% of the time. See what it is at SportsLine.
Who wins Rams vs. 49ers, and which side of the spread hits in over 50% of simulations? Visit SportsLine now to see which side of the 49ers vs. Rams spread you need to jump, all from the model that is 39-20 on top-rated picks since 2024, and find out.
