49ers vs. Bills Picks, Predictions & Player Props: Weather and Injuries to Play a Major Factor on Sunday Night

• Josh Allen is the current betting favorite to win the MVP award

• Brock Purdy is listed as questionable on the San Francisco 49ers injury report

• The 49ers defense ranks below league average in Def Rush DVOA, EPA, and Success Rate

After entering the year listed as one of the betting favorites to win the Super Bowl, the San Francisco 49ers have yet to spark a hot stretch of play as they are currently 5-6 and at the bottom of the NFC West division standings. Even at sub .500, the 49ers are actually still in contention for the division title as they are only one game back from the Seattle Seahawks. Unfortunately for San Francisco, injuries and poor weather will make it tough to get into scoring territory while against a stout Buffalo Bills defense.

49ers vs. Bills Odds 

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San Francisco 49ers vs. Buffalo Bills My Pick

• My Pick: 49ers Team Total Under 20.5 (-120) at BetMGM

Injuries have played a major factor towards the 49ers' struggles this year as their star players continue to rotate in and out of the lineup. Heading into Sunday, star left tackle Trent Williams is listed as out while Brock Purdy is questionable. Even if Purdy is good to go, getting into scoring territory will be a struggle for the 49ers' offense as they face off against a Bills defense who ranks seventh overall in Def DVOA and 10th in Def EPA while playing in harsh snowy weather conditions.

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49ers vs. Bills Predictions 

With the 49ers offensive line expected to regress while Trent Williams is out with an injury, Brock Purdy will find himself with less time in the pocket to let plays develop while also having to throw into low-quality passing lanes against a stout Bills secondary. Especially with Buffalo anchoring their linebackers at one of the heaviest rates in the league, hampering Purdy’s chances of racking up passing yards.

While the 49ers offense is expected to stall out, the Bills will have the opportunity to generate methodical drives down the field by attacking San Francisco’s struggles with stopping the run. The 49ers' inability to limit opposing rush production has been a thorn in their side all season long this year, giving the Bills James Cook the opportunity to routinely gash them for sizable gains at a time on Sunday night.

49ers vs. Bills Best Player Props

James Cook Over 62.5 Rushing Yards (-120 at BetMGM Sportsbook)

Stopping the run has been an issue for the 49ers' defense this season as they enter the contest ranked 21st in Def Rush DVOA, 23rd in EPA, 25th in Success Rate, and 19th Adjusted Line Yards. While poor weather normally gives a defense the ability to stack the box, the Bills Josh Allen is one of the few quarterbacks in the league whose arm is capable of negating poor weather. That forces the 49ers to stay stretched out in coverage, giving Cook high-quality running lanes for him to exploit.

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James Cook Over 16.5 Rush Attempts (-108 at FanDuel Sportsbook)

With Cook in a possession to succeed, as well as the 49ers second level of their defense being forced to stay stretched out in coverage, the Bills running back may receive an uptick in rush attempts as he will be their best path for success when on offense. Especially when in the red zone as keeping the ball on the ground helps negate the variance that comes with Allen’s arm while throwing into heavy coverage.

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Brock Purdy Under 230.5 Passing Yards (-113 at FanDuel Sportsbook)

With Purdy at less than 100% while nursing a shoulder injury, he will find it tough to generate pass production as he faces off against a Bills secondary who ranks 9th in Def Pass DVOA and 11th in EPA. Worse yet for Purdy, his starting left tackle and left guard are both out with an injury which leaves his blind side vulnerable. Factor in the poor weather and the 49ers may call a heavier dose of the run which also lessens the number of Purdy’s pass attempts to help clear the under on this prop.

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49ers vs. Bills How to Watch

• When: Sunday, December 1 at 8:20 PM ET

• Where: Highmark Stadium, Orchard Park, New York

• Where to Watch: NBC

49ers vs. Bills Best Promos and Sportsbooks

Take a look at some of the best NFL promos and top NFL betting sites available in the U.S. for Sunday night’s primetime matchup between the San Francisco 49ers and Buffalo Bills. Our favorites are listed in the table below.

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49ers vs. Bills Injuries

San Francisco 49ers

• QB Brock Purdy - Questionable

• LG Aaron Banks - Out

• LT Trent Williams - Out

• DE Nick Bosa - Out

• LB Dre Greenlaw - Out

Buffalo Bills

• WR Keon Coleman - Questionable

• TE Dalton Kincaid - Out

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