Week 5 is upon us, and Thursday Night Football is set up to be a good one from Inglewood, California. Kyle Shanahan and Mac Jones take their wounded San Francisco 49er crew on the road to take on Sean McVay, Matthew Stafford, and the Los Angeles Rams at So-Fi Stadium. Both teams sit at 3-1 atop the NFC West along with the Seattle Seahawks, and Arizona is just behind them in a tough division. Let’s take a look and make some picks for this Thursday Night Football game between the 49ers and Rams.
Thursday Night Football Picks and Best Bets: San Francisco 49ers at Los Angeles Rams
The San Francisco 49ers quite literally limp into this game about as beat up as one team can be. Before this week, 49er star players George Kittle, Brandon Aiyuk, and Nick Bosa were already on the Injured Reserve list, along with a host of other players. On Wednesday, it was announced that quarterback Brock Purdy would miss time again, after coming back last week and re-injuring himself against the Jaguars. Wide receivers Jauan Jennings, Ricky Pearsall, and Jordan Watkins, along with defensive end Robert Beal Jr, will all also miss Thursday night’s game. Defensive lineman CJ West is still listed as questionable.
Despite all this, San Francisco is still 3-1 on the year. They took care of business against NFC West opponent Seattle Seahawks in Week 1 on the road. Week 2 saw them hold off the New Orleans Saints on the road with Mac Jones as the starting quarterback. In Week 3, they went home and hosted a game for the first time in 2025 and snuck out of the game against the Arizona Cardinals with a one-point victory. Last week, Brock Purdy returned to the lineup. But, the 49ers fell at home against Trevor Lawrence and the Jacksonville Jaguars. That was the game where Purdy reaggravated his turf toe injury.
The Los Angeles Rams’ injury report is much shorter than that of their counterparts. Tight end Tyler Higbee is doubtful, as is offensive lineman Rob Havenstein. Outside of that, the Rams are a relatively healthy team coming into this Week 5 matchup. Like the 49ers and Seahawks from the NFC West, the Rams come into this one 3-1 and looking to gain more control over the division. They opened the season at home against the Houston Texans, where they won a defensive shootout 14-9. Week 2 took them to Nashville to play against a horrible Titans team, and they took care of business. In Week 3, they went to the Super Bowl Champion Philadelphia Eagles and played them tough, ultimately losing 33–26. Last week, the Colts came into So-Fi, and the Rams were once again the best team.
These two head coaches, who once worked together on the Washington (Redskins at the time) coaching staff, have squared off 17 times as head coaches for these respective teams. They’ve almost taken turns dominating each other through the years. Sean McVay and the Rams won three of the first four meetings. Then Kyle Shanahan and the 49ers went on a dominating run, winning six games in a row against the Rams, and nine of 10. Even in 2019, when the Rams made the Super Bowl, they lost both games to the 49ers. The year they won, they also lost both regular-season games to them, but got revenge in the NFC Championship game. Last year, the Rams flipped the script, winning both games against San Francisco, as well as their last matchup in the 2023 season, bringing the record to 10-7 in favor of Kyle Shanahan.
Thursday Night Football Picks and Best Bets: San Francisco 49ers at Los Angeles Rams
Christian McCaffrey 8+ Receptions (+140)
Honestly, McCaffrey is about the only player left for the 49ers. Has he been siphoning other players’ health, or what’s going on in San Francisco? Who knows. What I do know is that they are going to have to get the ball in this man’s hand if they want any chance of keeping this game close. The Rams will likely do everything they can to shut down the game. So, the 49ers are going to have to use the passing game to get the ball into their explosive playmakers’ hands in space.
Mac Jones isn’t 100% healthy himself, as the backup has been dealing with a knee injury. He’s good to go for Thursday, but it could hamper him. The Rams are going to be all over Jones when he does drop back, and with everyone hurt, he’s got to get the ball to McCaffrey and let him work his magic. McCaffrey has had at least six receptions in each game, with 9+ in two of the four games.
Kyren Williams Over 68.5 Rushing Yards (-115)
Outside of Week 1, when the 49ers were somewhat healthy, their rush defense has been atrocious. In Week 2, behind a horrible New Orleans offensive line, Alvin Kamara ran for 99 yards against the 49ers, even in a loss. In Week 3, James Connor and then Trey Benson, who took over after the Connor injury, ran for 64 yards against the 49ers, and Kyler Murray added another 37.
Last week, Travis Etienne ran all over this beat-up defense for 124 yards on the Jaguars’ way to a victory. I also love Kyren over 14.5 yards for his longest rush, something the 49ers have given up in three of the four weeks. The Rams, on a short week against a beat-up defense, are going to run the ball down the 49ers’ throats.
Los Angeles Rams -6.5 (-157)
This one is simple for me. This 49ers team has found a way to piece things together through the first 4 weeks to get to 3-1. Now they play the toughest team they’ve faced, and they are the most injured they’ve been. Also in those patterns above, we’re currently in the McVay winning games portion of things, as the Rams hold a three-game win streak against the 49ers. The Rams are the better team and much, much healthier than the 49ers. Getting them at just under a touchdown here is amazing. Even if you only have a -7.5 option, I’d still take it. The Rams roll in this game.
