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Story summary
- The San Francisco 49ers (2-0) will face the Arizona Cardinals (2-0) on September 21, 2025, at Levi's Stadium, Santa Clara, CA.
- The 49ers are slight favorites with a spread of -2.5 and a moneyline of -162; the Cardinals are at +136.
- Both teams have strong offenses, with the 49ers averaging 21.5 points per game and the Cardinals 23.5.
- Injuries impact both teams, especially the 49ers' receivers and the Cardinals' secondary.
- Recent matchups favor the Cardinals, who swept the 49ers last season.
