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The Arizona Cardinals visit the San Francisco 49ers on Sunday, September 27, 2026 at 4:05 p.m. ET from Levi’s Stadium, Santa Clara, CA. Arizona is 1-1 after a 31-7 loss to Seattle and San Francisco is 2-0 after a Week 2 win over Miami.
San Francisco averages 31 points and 380.5 yards per game and ranks among the league leaders on third down. Arizona averages 16.5 points per game with 179 passing yards and 93 rushing yards per game.
San Francisco allows 10 points per game with 4 sacks. Arizona allows 22.5 points per game and carries a plus-2 turnover margin.
The 49ers are 8.5-point favorites over the Cardinals.
Below, we’ll give you all the details you need to know about how to watch this game.
How to Watch Cardinals vs. 49ers
Players To Watch
San Francisco has not allowed Purdy to be sacked through two games, the cleanest start to a season in franchise history. He has answered by throwing for 492 yards and 5 touchdowns, and the 49ers are averaging 31 points and 380.5 yards per game with him running the offense.
Arizona’s defense has allowed 22.5 points per game, and San Francisco already ranks among the league’s best on third down. That combination puts real weight on how fast Purdy can turn drives into points rather than just yardage.
Arizona’s passing game has really only produced one consistent piece through two weeks, and it is the tight end. McBride has caught 17 of 22 targets for 136 yards and 2 touchdowns, scoring in both of the Cardinals’ first two games, including 8 catches for 41 yards in last week’s loss to Seattle.
San Francisco’s defense has allowed just 10 points per game this season, third-fewest in the league, which makes McBride’s underneath targets one of the few dependable ways Arizona can move the chains against it.
Christian McCaffrey reached 100 career regular-season touchdowns by scoring twice in the 49ers’ Week 2 win over Miami, each from a yard out. He finished that game with 10 carries for 23 yards and 4 catches for 43 yards, and San Francisco is now averaging 134.5 rushing yards per game with 3 rushing touchdowns on the season.
Arizona has given up 6 total touchdowns on defense through two games, and McCaffrey’s role near the goal line gives San Francisco a direct way to keep testing that same soft spot again Sunday.
San Francisco’s defense already has 4 sacks through two games, and Brissett is walking into that pressure after a Week 2 outing that produced just 95 yards passing in a 31-7 loss to Seattle. He has 372 yards and 2 touchdowns on the season, with an interception in that same Seattle game he would rather forget.
Arizona’s plus-2 turnover margin is the one real edge working in his favor, built more by the defense forcing takeaways than by anything Brissett has generated through the air. Holding onto that margin will matter against a 49ers front that already has him at a disadvantage.
Cardinals vs. 49ers Odds
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