The Niners won the earlier matchup at home, 24-16 in Week 6, after started fast with a 21-6 at halftime lead. Jimmy Garoppolo passed 23-of-33 for 268 yards and three touchdowns in the win while Jared Goff passed for only 198 yards and an interception. Of course, each team's roster for this one could be drastically different due to all those injuries.
San Francisco had one of the latest byes in the league, and it worked out because the Niners were one of the most banged-up teams in the country. Two weeks ago, the team lost 27-13 at New Orleans and finished a stretch of three of four on the road against the Pats, Seahawks, and Saints with the home game being against the Packers. Nick Mullens was under center for the third straight game, but he got little help from the rest of the offense and the defense had their struggles.
It's a short week for the Rams, which were just in Tampa Bay on Monday night for a 27-24 win. The team has won two one-score games since their Week 9 bye. Goff was fantastic in the win feeding both Robert Woods and Cooper Kupp as he nearly cracked the 400-yard passing mark. The Rams defense also harassed Tom Brady into a couple of interceptions as they moved to 7-3 on the season.
San Francisco at Los Angeles
Kickoff: Sunday, Nov. 29, 4:05 p.m. ET
Spread: Rams -6.5
Three Things to Watch
As noted earlier, the Niners are coming off their bye week and hopefully will have some of their walking wounded back on the field. Schedule-wise this is their fourth road game over the last six weeks. They'll have two straight at home after this against Buffalo and Washington. On the Rams side, it's a short week after playing on Monday night on the road. I think that rest differential will be a factor early on. This is an LA team that has played two high-profile games and will take on the Cardinals and Patriots in the next two weeks. Maybe we see a slow start.
2. Walking wounded return?
The Rams have had some of the best injury luck in the league. The Niners, meanwhile, have had some of the worst. There's good news, though, as both Deebo Samuel and Tevin Coleman returned to practice on Wednesday. Samuel had a hamstring injury in Week 7, and Coleman aggravated an injury in Week 8 that he originally had in Week 2. Raheem Mostert and Jeff Wilson Jr. had their 21-day practice window activated while Richard Sherman is working his way back from a calf injury that has kept him out since the season-opener. It wasn't all great news for San Francisco, though, as six players still remain on the reserve/COVID-19 list, including Trent Williams and Brandon Aiyuk. Even if a couple of these guys return, this should be a competitive contest.
3. The coaching matchup
Two of the brightest offensive minds in football go against each other as Sean McVay takes on Kyle Shanahan. These are two of the few coaches I'd trust most to look at their opponent over a two-week span and figure out the best ways to exploit them. There are not a lot of holes in the Rams defense, especially with the amount of pressure they put on the quarterback. San Francisco will need to keep whoever is under center upright. It'll be interesting if there are new wrinkles coming from the San Francisco offense in this one. It'll be a good chess match between McVay and Shanahan, even though only one of them has all his pieces.
I expect a slow start for LA and a closer than normal game here. I think San Francisco gets some of its offense back and makes things interesting. Still, they'll fall short as the Rams defense makes a key stop at the end.
Prediction: Rams 24, 49ers 20
— Written by Matt Josephs, who is a part of the Athlon Sports Contributor Network. Follow him on Twitter @MidMajorMatt.