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49ers vs. Bills Sunday Night Football Start 'Em, Sit 'Em: Brock Purdy, Josh Allen, Christian McCaffrey, Amari Cooper, Jauan Jennings, and more

2025 Fantasy Football Early-Round Best Ball Busts, Overvalued

Fantasy football start 'em, sit 'em, and lineup advice for the 49ers vs. Bills on Sunday Night Football in Week 13 (2024). Detailed player breakdowns and matchup analysis.

It's been an exciting week filled with holiday football and we have an excellent matchup for Sunday Night Football between two of the league's most interesting teams, as the San Francisco 49ers travel to Buffalo to tangle with the Bills.

Plagued by injuries throughout 2024, it feels like do-or-die time for the Niners, who enter Week 13 with a record of 5-6. Meanwhile, the Bills appear to be cruising toward an AFC East title at 9-2. Both squads feature several impactful fantasy performers.

We'll be bringing you Sunday Night Football analysis all year long, focusing on who to definitely start, who is on the fence, and who should find the bench. Let's dive into this awesome Sunday Night matchup. You can also read all Week 13 Matchups for the entire slate. Good luck, RotoBallers!

Be sure to check all of our fantasy football rankings for 2025:

 

San Francisco 49ers at Buffalo Bills - 8:20 pm ET

Spread: Bills -6.5

Total: 44.5

 

Matchup Outlooks

Matchups We Love:

RB Christian McCaffrey 

Christian McCaffrey has surely struggled on the ground in his first three games of the season. He is averaging only 3.47 yards per carry and 13 PPR fantasy points per game. But this could be the week we see McCaffrey put up his usual big fantasy numbers. The Bills have allowed the third-most fantasy points per game to running backs this season, making the 49ers playmaker a must-start option.

RB James Cook 

James Cook has been a touchdown machine for the Bills this season, scoring 11 touchdowns over the last nine games. With a matchup against the 49ers in Week 13, Cook will be a strong RB2 play. San Francisco has allowed five top-12 fantasy running back finishes over the last six games, and Josh Jacobs just finished with 28.6 PPR fantasy points against this defense last week.

Matchups We Hate:

QB Brock Purdy 

It remains to be seen if Brock Purdy (shoulder) will play in Week 13. If he does, he will be a low-end QB1 option against a tough Bills secondary. Buffalo has given up the eighth-fewest fantasy points per game to opposing quarterbacks, and only one quarterback has finished as a top-12 option against this secondary this year. If Purdy can't go, then Brandon Allen should only be started in deeper Superflex leagues.

Update: Purdy is questionable for Sunday. However, he is expected to play. 

WR Khalil Shakir 

Khalil Shakir has been one of the more consistent wide receivers in fantasy this year, as he has scored between 10 and 15 PPR fantasy points in eight of 10 games. However, he'll be a riskier flex option in Week 13 against a 49ers defense that has allowed the fewest fantasy points per game to slot wideouts this season.

Other Matchups:

QB Josh Allen 

Josh Allen will return from the bye and continue to be a solid QB1 option in Week 13. Even though the 49ers have not allowed a top-14 fantasy quarterback in six straight games, Allen's rushing upside makes him a must-start in all lineups this week. He has rushed for at least 50 yards and a touchdown in back-to-back games.

49ers WRs

Whether you should play Deebo Samuel Sr. and Jauan Jennings this week will depend if Purdy can suit up. If he does, Samuel will come in as a high-end WR3. As for Jennings, he'll be a WR2 option after finishing with over 16 PPR fantasy points in both Week 10 and Week 11 with Purdy. If Allen starts for the 49ers this weekend, though, Samuel will be a risky flex play, while Jennings will fall to WR3 territory.

Update: Purdy is questionable for Sunday's game but is expected to play in Week 13. So, plan accordingly for both Samuel and Jennings. 

WR Amari Cooper 

Amari Cooper has not been a strong fantasy option since being traded to the Bills. He has played under 55% of the team's offensive snaps in all three games while catching only three passes combined over the last two contests. He will be a risky flex play in 12-plus team leagues this weekend against a 49ers defense that has allowed the ninth-fewest fantasy points per game to opposing wideouts this season.

TE George Kittle 

George Kittle is the only tight end this year to finish top-10 in every game this season. As a result, he will continue to be a must-start option in Week 13 against the Bills. Even with Brandon Allen starting last week, Kittle reeled in six passes for 82 yards and one touchdown. He should be in all lineups this weekend

Fantasy-Relevant Injuries: 



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