Brock Purdy, 49ers Injuries Cause Massive Shift in 49ers vs. Rams Odds for Week 5

The 49ers are massive road underdogs in Week 5.

San Francisco 49ers quarterback Brock Purdy has been ruled out for Week 5, shifting the betting odds against the Rams. / Kyle Terada-Imagn Images

The San Francisco 49ers offense is down several key players, including starting quarterback Brock Purdy for Week 5 against the Los Angeles Rams on Thursday Night Football.

The 49ers have officially ruled out Purdy, Jauan Jennings and Ricky Pearsall while George Kittle (injured reserve) and Brandon Aiyuk (PUP) are unable to suit up as well. As a result, the 49ers will start Mac Jones for the third time in the 2025 season in Week 5.

Oddsmakers have been shifting the spread for the 49ers-Rams clash all week long, but with the official injury reports coming out, it appears to have settled at 49ers +8.5.

On Sunday night, the 49ers opened up as three-point underdogs against the Rams, but that number has been steadily climbing in favor or Los Angeles.

On Monday, Kyle Shanahan expressed concern for Purdy's availability, saying that his tur toe injury was bothering him after Sunday's game. With such a quick turnaround for the 49ers, oddsmakers shifted the spread in this game by 2.5 points.

Then, when Purdy, Jennings and Pearsall all did not practice on Tuesday, the spread shifted all the way to Rams -7 on Wednesday before making a final move to Rams -8.5 at DraftKings as of Thursday morning.

A 5.5-point swing in any game is massive, but it makes sense since San Francisco won't have it's top two receiver and starting quarterback. Jones has been solid in relief of Purdy, throwing for 563 yards, four touchdowns and just one pick while leading San Francisco to a 2-0 record.

However, he did throw three of those scores in a win over the New Orleans Saints. The 49ers are 3-1 this season, but they're facing an uphill battle to win this matchup, as the Rams are 2-0 against the spread as home favorites in 2025 and 91-58 straight up at home in the Sean McVay era.

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Odds refresh periodically and are subject to change.

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