The 49ers are battling injuries as they face the Bills after losing two consecutive games; star players like Nick Bosa and Trent Williams will not play.
With Brock Purdy returning from a shoulder injury, the Niners hope to turn their losing streak around against the Bills, who are riding a six-game winning streak.
The Bills, led by MVP candidate Josh Allen, come off a bye week confident after recently beating the Chiefs and look to extend their dominance.
Lake-effect snow and freezing temperatures are set to affect the game, with nearly 22.9 inches of snow reported in Orchard Park before kickoff.
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