Cardinals vs. 49ers odds: Opening lines for Week 3 matchup
Sep 20, 2026; Glendale, Arizona, USA; Arizona Cardinals quarterback Jacoby Brissett (7) is tackled by Seattle Seahawks linebacker Drake Thomas (32) in the second quarter at State Farm Stadium. Mandatory Credit: Matt Kartozian-Imagn Images | IMAGN IMAGES via Reuters Connect

For the Arizona Cardinals, a week in the sunshine may have burned them.

Maybe not for the season, but the week two loss to the Seattle Seahawks was a nasty reminder of how far away from the top they are.

Our friends at FanDuel Sportsbook baited a lot to take the Cardinals to cover the 4.5-point spread heading into Sunday’s matchup… that doesn’t seem to be the case with their opening line for week three.

The Cardinals will take on the 2-0 San Francisco 49ers in week two, and FanDuel Sportsbook has the Cardinals as 8.5-point underdogs ahead of the Sunday matchup.

As far as lines go, that is only the second biggest underdog of the week, just trailing the Dolphins as 10.5-point dogs ahead of their matchup with the Chiefs.

The Cardinals can definitely get some of their reputation back with a strong performance against the Niners, but everyone, including the sharps want to see it before they believe it.

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