Can the Rams Get Revenge Against an Even More Injured 49ers Team?

In Week 10 of the 2025 NFL Season, the San Francisco 49ers and the Los Angeles Rams are set to match up for their second contest of the year. In Week Five, the 49ers overcame a multitude of injuries to beat the Rams 26-23 in overtime. This victory was led by backup quarterback Mac Jones and 142 receiving yards from Kendrick Bourne. The big thing that made headlines was the way Los Angeles lost this game. Between a fumble on the goal line, a blocked field goal, and getting stopped on fourth and one while in position to score in overtime, the Rams’ own mistakes were what cost them a close game. Now in Week 10, this huge upset has to be looming in the minds of all the players and coaches on both sidelines.

​Los Angeles Offense vs. San Francisco Defense

On this side of the ball, a few things are different from Week Five about both teams. First of all, the 49ers are somehow more injured. San Francisco was already without Nick Bosa in the first game, but they will now be without Fred Warner, who went down with a season-ending ankle injury in Week Six’s loss to the Buccaneers. With the two pinnacles of their defense gone, as well as Mykel Williams likely being out, the 49ers’ defense is now a shell of itself, but that doesn't mean they’re completely out for the count. The 49ers have secured two wins since losing Warner, notably holding the Falcons and the Giants to 10 and 24 points, respectively. Bryce Huff stepped up as a pass-rush disruptor against Atlanta. Huff is on the injury report, but has been back in practice on limited participation, and his potential return will be huge as he is the main man to watch in this matchup. San Francisco will need to slow down the Rams’ passing game as Matthew Stafford has been lethal thus far this year. Stafford has been amazing against the blitz this year, and San Francisco hasn’t been amazing at getting to the quarterback in blitzes either, so they will have to rely on Huff and their four-man rush to put pressure on the offense.

​The Rams’ offense also has a couple of major differences since the last time they played. The first difference is that Steve Avila and Rob Havenstein, on the offensive line, have returned from injury. The other big difference is that the Rams have slightly shifted some of their offensive game since last playing the 49ers. When they played San Francisco, Los Angeles was leaning heavily on their two best receivers, Puka Nacua and Davante Adams. When Nacua went down with an injury in Week Six, the Rams had to shift their offense to bolster some of their other talented receiving threats. Now in Nacua’s return, the Rams are able to be far more dynamic and balanced in the ways that they attack defenses through the air, with their tight end room in particular stepping up and making contributions. In Los Angeles’ last two games, all four tight ends, Tyler Higbee, Colby Parkinson, Davis Allen, and Terrance Ferguson, have gotten involved in the passing game, and leaning on these bigger bodies as receivers has opened up Nacua and Adams to still be effective with less of a burden placed on them. Nacua was banged up coming into this week, but practiced in full on Thursday, and should likely be available to play. Adams has developed a beautiful red zone connection with Stafford, which just wasn’t working in the last matchup, and could be a difference maker this week. These differences are on top of a balanced run game that Kyren Williams excelled in for the last matchup. This side of the ball will be where the Rams have the largest advantage over the 49ers, especially with the injuries that have plagued San Francisco.

San Francisco Offense vs. Los Angeles Defense

On this side of the ball, San Francisco still can’t avoid the injury reports. Their starting quarterback, Brock Purdy, is a limited participant in practice for the third week in a row with a turf toe injury. While he might play, this is the same story as the past few weeks, and he could very well be out again. Ricky Pearsall has also not been practicing and is in line to miss his sixth week in a row. Even if Jones has to play, it’s not all bad. He beat the Rams once and has been effective thus far this year, with a 3-2 record in his starts. He also has Jauan Jennings and George Kittle as receiving weapons this time around. The offensive line kept Jones well protected last time, and could very well do this again, even against a very scary Rams pass rush. While the Rams have been very good against the running game, Christian McCaffrey was still super effective in the passing game, and will likely repeat this process again.​

Los Angeles got carved up by Jones through the air last game, and will be looking to prevent that from happening this time around. The Rams have improved in their secondary since Week Five. They traded for Roger McCreary before the trade deadline, though he hasn’t yet played defensive snaps since he’s getting used to the defense. He could get playing time in this game, and we will see how effective he can be in Los Angeles’ scheme. On top of what McCreary can contribute, Emmanuel Forbes, who got diced up in the last matchup, has been playing significantly better in recent weeks and gets a chance to redeem himself in this week’s game. Poona Ford, Kobie Turner, Nate Landman, and the interior defense have been so effective against the run, and thus the battle between Mac Jones and the Rams’ pass rush and secondary will be the main thing to watch on this side of the ball. Especially because McCaffery on the other side is such a pass catcher, expect the 49ers to try to attack through the air, and try to test guys like Forbes or Darious Williams coming off an injury.

​Special Teams/Coaching

Just a short note that is worth mentioning is that San Francisco will have a rare special teams advantage going into this game. Their blocked field goal last game helped win the game, and costly mistakes in the Rams’ special teams have been a thorn in their side all season. The Rams have made some practice squad moves to try to address the kicking issues, but Joshua Karty will likely still be the starter. Karty could be a weakness for the Rams team, missing out on key extra points that might be the difference in a tight division game. One last important note is the coaching matchup, where Kyle Shanahan seems to just have Sean McVay’s number, with an 11-7 record against him. Every time these two teams meet, this coaching battle between two of the league's top minds will be a sight worth watching.