Which 49ers stars won't play against the Rams on Thursday night?

The San Francisco 49ers enter their Thursday night showdown against the Los Angeles Rams at a significant disadvantage. Oddsmakers at BetMGM have listed the 49ers as 8.5-point underdogs, and much of that is due to their growing injury concerns.

The stakes are high—whoever wins this Week 5 clash will stand alone atop the NFC West. But San Francisco will be missing several of its biggest names when they take the field at SoFi Stadium.

The most notable absence is quarterback Brock Purdy, who has already missed two games this season with a toe injury. Purdy returned last weekend against the Jacksonville Jaguars but experienced soreness that forced him back to the sidelines.

As a result, Mac Jones will make his third start of the year. Jones has already led the 49ers to victories over the New Orleans Saints and Arizona Cardinals, but this will be his toughest test yet.

Unfortunately for Jones, he won't have two of his most reliable weapons. Rookie wideout Ricky Pearsall suffered a knee injury against Jacksonville, while veteran receiver Jauan Jennings continues to battle an ankle injury compounded by a rib injury. That leaves the 49ers' receiving corps thin for a prime-time divisional matchup.

Adding to the challenge, star tight end George Kittle remains on injured reserve with a hamstring injury. He is not eligible to return until Week 6 against the Tampa Bay Buccaneers, leaving San Francisco without one of its most dependable offensive playmakers.

On defense, the injuries have been just as costly. Defensive tackle C.J. West is questionable with a thumb injury, while defensive end Robert Beal has been ruled out with an ankle issue. Most devastating of all, the 49ers are still adjusting to life without Nick Bosa, who suffered a season-ending ACL tear in Week 3. Without their star pass rusher, San Francisco managed just five pressures, no sacks, and no quarterback hits against Jacksonville.

The 49ers' defense will need to step up in a big way. San Francisco has forced only three takeaways this season, a mark that ranks among the league's lowest. Compounding the problem, the offense has committed eight giveaways—tied for the most in the NFL.

The 49ers are battered, undermanned, and facing a red-hot division rival on the road. If San Francisco hopes to upset the Rams and reclaim momentum, Mac Jones and the defense must deliver their best performance of the season.