Game Info
Kickoff: Sunday, September 21, 2025, 4:25 p.m. ET
Location: Levi’s Stadium, Santa Clara, CA
Network: FOX
Game at a Glance
Arizona travels to play San Francisco with both teams entering undefeated.
Arizona Cardinals
Quarterback
Kyler Murray: SIT, QB2 (startable in Superflex)
Kyler Murray has performed through two starts this season, which is best described as mild. He hasn’t been bad, but he hasn’t done anything spectacular either. Murray has a 3:1 touchdown to interception ratio, but has 383 total passing yards. Up next is the Niners, who’ve allowed the fifth-fewest fantasy points to opposing quarterbacks. He’s a borderline start in 1QB leagues, but I’d prefer to sit him if you have other options.
Running Back
James Conner: START, RB2
Trey Benson: FLEX, RB3
James Conner is still the Cardinals’ lead back, but I doubt that lasts the whole season. Conner has 23 rushing attempts to Trey Benson‘s 11, but Benson has rushed 10 more yards. That’s thanks to his 7.55 yards per carry, which tops the NFL among backs with at least 10 carries. Conner remains a solid RB2 as long as he maintains his lead role. But Benson is set to take over before long, and has standalone flex value until the takeover occurs.
Wide Receiver
Marvin Harrison Jr.: START, WR2
Zay Jones: SIT
Michael Wilson: SIT
Marvin Harrison Jr. couldn’t replicate his big Week 1 performance, finishing with two catches for 27 yards against the Panthers. His status as the Cardinals’ WR1 keeps him in the WR2 range, but he could disappoint again against a Niners defense that’s allowing just 8.7 yards per reception.
Tight End
Trey McBride: START, TE1
You don’t need me to tell you to start Trey McBride. But did you know he became an avid golfer after being drafted to the Cardinals?
Defense/Special Teams
Arizona Cardinals: STREAMER
If Mac Jones starts, the Cardinals are a decent streamer. If Brock Purdy returns, the Cardinals are best left on the bench.
San Francisco 49ers
Quarterback
Mac Jones: SIT, QB2 (Startable in Superflex)
Brock Purdy: Unlikely to play, but START, QB1 if active.
It was announced on Wednesday afternoon that Brock Purdy got in a limited practice and has a chance to return after missing just one week. I think the 49ers hold him out at least one more week, but you never know with Kyle Shanahan. Mac Jones is startable in Superflex, but that’s it. If Purdy does start for the 49ers, he does the same for your fantasy team.
Running Back
Christian McCaffrey: START, RB1
Brian Robinson Jr.: FLEX, RB4
Isaac Guerendo: SIT
You don’t need me to tell you start Christian McCaffrey. But did you know his favorite snack is Cool Ranch Doritos?
Wide Receiver
Marquez Valdes-Scantling: SIT
Ricky Pearsall: FLEX, WR4
Jauan Jennings: START, WR3
Ricky Pearsall has been mostly disappointing considering the opportunity presented with all the injuries in San Fransico and the preseason hype surrounding him. He’s no more than a flex. Jauan Jennings was the top option for Jones and likely remains the same if Purdy returns. He’s a borderline WR3 regardless of who’s under center.
Tight End
Jake Tonges: SIT
Until the return of George Kittle, you’re not starting any 49ers tight end.
Defense/Special Teams
San Francisco 49ers: STREAMER
The 49ers D/ST is a solid streamer based on sack and turnover potential.