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Come Fan with UsFriday, June 26, 2026

NFL odds and lines Week 17: Cardinals vs. 49ers

The San Francisco 49ers open as heavy favorites against the struggling Arizona Cardinals in Week 17.

Stephen Brashear

The San Francisco 49ers opened as 16.5-point favorites against the visiting Arizona Cardinals in Week 17 action, according to OddsShark.com. The spread has held somewhat steady, but in some instances it has increased by a point in favor of the 49ers.

The game on Sunday at Candlestick Park will be about the run game. The Cardinals sit in the bottom five in the league in rushing yards allowed per outing, and that should be concerning considering the 49ers are fourth in the NFL in rushing yards per game.

San Francisco has gone 13-3 straight up in the last 16 home games against the Cardinals, and Arizona is only 1-10 straight up and 3-7-1 against the spread in its last 11 games.

The total opened at 38.5 points. Arizona’s total has gone over in the past four games as it has allowed games to get out of hand, while San Francisco has seen the total go over in six of its last seven.

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