Brock Purdy Injury Uncertainty Shifts 49ers vs. Rams Odds for Thursday Night Football

The San Francisco 49ers are now 5.5-point underdogs in Week 5 against the Los Angeles Rams.

San Francisco 49ers quarterback Brock Purdy is dealing with a toe injury that has moved the odds for the 49ers-Rams matchup. / Kyle Terada-Imagn Images

San Francisco 49ers quarterback Brock Purdy has missed two games in the 2025 season with a turf toe injury, and he appears to be up in the air for Week 5 against the Los Angeles Rams on Thursday night.

Purdy played in the 49ers' loss to the Jacksonville Jaguars in Week 4, but he came out of the game with soreness in his toe, according to head coach Kyle Shanahan. That has moved the odds for Thursday's game in a big way at DraftKings.

After opening as three-point underdogs in this Week 5 matchup, the 49ers are now 5.5-point underdogs -- a massive 2.5-point shift since the odds for this game were released on Sunday night.

#49ers HC Kyle Shanahan says QB Brock Purdy reported toe soreness after last night’s game. He’ll be re-evaluated later today.

SF has a short week with a TNF game vs. the Rams coming up. pic.twitter.com/5ma9NhzOuQ

— Ari Meirov (@MySportsUpdate) September 29, 2025

This could be a sign that Vegas is unsure whether or not Purdy is going to play on Thursday. It doesn't that this game is on a short week for the Rams and 49ers, as it may make it tougher for Purdy to manage his foot and be ready to go.

Both the Rams and 49ers are 3-1 in the 2025 season, although the Rams are +125 favorites to win the NFC West this season. San Francisco (+170) is second in the odds.

Purdy played decently in Week 4 against Jacksonville, throwing for 309 yards and two touchdowns, but he was also picked off twice. In just two appearances this season, Purdy has been picked off four times.

If Purdy is unable to play in Week 5, the 49ers would likely turn to backup Mac Jones, who led the team to a 2-0 record in Weeks 2 and 3 this season. The Rams, who are 2-0 against the spread as home favorites this season, may end up being favored by even more if Purdy is officially ruled out.

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Odds refresh periodically and are subject to change.

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