NFL: Los Angeles Rams at Philadelphia Eagles
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Early control of the NFC West will be on the line when the San Francisco 49ers take on the Los Angeles Rams on Thursday Night Football. San Francisco dropped a 26-21 decision to Jacksonville, while Los Angeles pulled out a 27-20 win over Indianapolis on Sunday. The Rams (3-1), who are 0-1 in the conference, are 2-0 on their home field this season. The 49ers (3-1), who are 3-0 in the conference, are 2-0 on the road. San Francisco quarterback Brock Purdy (toe) has been ruled out, along with Jauan Jennings (ankle, ribs) and Ricky Pearsall (knee), while George Kittle (hamstring) remains on IR.

Kickoff from SoFi Stadium in Inglewood, Calif., is set for 8:15 p.m. ET. The 49ers lead the all-time series 78-71-3, including wins in each of the last five meetings. After opening at -1.5, the Rams are now 8.5-point favorites in the latest 49ers vs. Rams odds, while the over/under for total points scored is 43.5, marking a 4-point drop. L.A. is at -455 on the money line, with San Fran at +350. Before making any Rams vs. 49ers picks, make sure to check out the Thursday Night Football predictions from SportsLine NFL expert Larry Hartstein.

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A former lead writer for Covers and The Linemakers, Hartstein combines a vast network of Vegas sources with an analytical approach he honed while working for Pro Football Focus. Hartstein tied for 52nd place (out of 1,598 entries) in the 2022 Westgate Las Vegas SuperContest, going 53-34-3 ATS. He is coming off a down 2024 NFL season at SportsLine that puts him at 967-821 all-time on NFL sides and props (plus 13.8 units), including 593-518 ATS. Entering the 2025-26 season, he has been profitable in five of six seasons, going 659-564 ATS (plus $3,556 for $100 players). 

In addition, Hartstein has gone 25-10 on his last 35 picks involving the Rams, returning more than $1,400. Anybody following his NFL betting picks at sportsbooks and on betting sites could have seen strong returns. 

Now, Hartstein has set his sights on 49ers vs. Rams and just locked in his picks and predictions. You can head to SportsLine now to see his picks. Here are several NFL odds and betting lines for 49ers vs. Rams:

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 -455, San Francisco +350

49ers vs. Rams picks

See picks at SportsLine

49ers vs. Rams streaming 

Amazon Prime

Why the Rams can win

Veteran quarterback Matthew Stafford powers the Los Angeles offense. In four games, he has completed 92 of 136 passes (67.6%) for 1,114 yards and eight touchdowns with two interceptions for a 106.1 rating. In Sunday's win over the Colts, he completed 29 of 41 passes (70.7%) for 375 yards and three touchdowns. He completed 23 of 33 passes (69.7%) for 298 yards and two touchdowns with one interception in a 33-19 win over the Tennessee Titans on Sept. 14.

His top target is third-year veteran wide receiver Puka Nacua. He leads the Rams with 42 receptions for 503 yards (12.0 average) and one touchdown. He has eight explosive plays of 20 yards or more, including a long of 31, with 170 yards after the catch and 26 first-down conversions. In the win over the Colts, he caught 13 passes for 170 yards and one touchdown. See which team to back at SportsLine. 

Why the 49ers can win

With Purdy ruled out, Mac Jones will get the nod. Jones has played in two games, completing 53 of 80 passes (66.3%) for 563 yards and four touchdowns with just one interception. In a 26-21 win over the New Orleans Saints on Sept. 14, he completed 26 of 39 passes (66.7%) for 279 yards and three touchdowns.

Leading the rushing attack is veteran running back Christian McCaffrey. In four games this season, he has carried 69 times for 225 yards (3.3 average), while catching a team-high 31 passes for 305 yards and two touchdowns. He has had four explosive plays of 20 yards or more, including a long of 29. In Sunday's loss to Jacksonville, he carried 17 times for 49 yards, while catching six passes for 92 yards and one touchdown. See which team to back at SportsLine.

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How to make 49ers vs. Rams picks

Hartstein has analyzed 49ers vs. Rams from every angle and he's leaning Under on the point total. He has also discovered a critical X-factor that has him jumping all over one side of the spread. He's only sharing what it is, and which side to back, at SportsLine.

Who wins 49ers vs. Rams, and what critical X-factor makes one side of the spread a must-back? Visit SportsLine now to see which side of the 49ers vs. Rams spread you need to jump on, all from the expert that is 25-10 on his last 35 Los Angeles Rams picks, and find out.