The San Francisco 49ers visit the LA Rams in a marquee divisional matchup on Thursday Night Football at SoFi Stadium in Inglewood, California.

The Niners laundry list of injuries finally caught up with them this past weekend as Trevor Lawrence and the Jaguars handed Kyle Shanahan’s squad their first loss. Jacksonville jumped out to a 17-6 lead at halftime and the 49ers really never threatened a comeback in the second half.

USA Today's NFL experts make their picks for a Week 5 showdown between the Los Angeles Rams and San Francisco 49ers

The Los Angeles Rams and San Francisco 49ers are both 3-1 in the 2025 season entering a crucial Week 5 matchup on Thursday Night Football.  Los Angeles pulled o

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.

The San Francisco 49ers travel to Los Angeles on Thursday night hoping an injury-riddled offense can hold up against the Rams' ninth-ranked defense.

Preview the Week 5 matchup between the Los Angeles Rams and San Francisco 49ers with predictions, odds, over/under, spread, betting lines and more.