Cardinals vs. 49ers Prediction, Odds, Spread, Injuries, Trends for NFL Week 5 (How to Bet Total)

Betting odds, pick and prediction for the Arizona Cardinals-San Francisco 49ers matchup in NFL Week 5.

San Francisco 49ers wide receiver Deebo Samuel Sr. / Brad Rempel-Imagn Images

The San Francisco 49ers bounced back from back-to-back losses, dominating the New England Patriots in Week 4 to get back to .500.

In Week 5, Brock Purdy and company will take on the Arizona Cardinals, who have been awful defensively this season and sit at 1-3. 

Arizona was blown out — at home — by the Washington Commanders in Week 4, and it is a major underdog in Week 5. 

With the 49ers looking to get back to the No. 1 spot in the NFC, here’s a breakdown of the odds, players to watch and my best bet for Sunday’s matchup. 

Cardinals vs. 49ers Odds, Spread and Total

Odds via DraftKings Sportsbook.

Spread

• Cardinals +7.5 (-115)
• 49ers -7.5 (-105)

Moneyline

• Cardinals: +275
• 49ers: -345

Total

• 49.5 (Over -112/Under -108)

Cardinals vs. 49ers How to Watch

• Date: Sunday, Oct. 6
• Time: 4:05 p.m. EST
• Venue: Levi’s Stadium
• How to Watch (TV): FOX
• Cardinals record: 1-3
• 49ers record: 2-2

Cardinals vs. 49ers Betting Trends

• The Cardinals are 2-2 against the spread this season.
• The 49ers are 2-2 against the spread this season.
• San Francisco is 2-0 against the spread at home this season.
• The OVER is 3-1 in the 49ers’ games this season.
• The OVER is 3-1 in the Cardinals’ games this season. 

Cardinals vs. 49ers Injury Reports

Cardinals Injury Report

• Trey McBride – questionable
• Khyiris Tonga – questionable

49ers Injury Report

• Chris Conley – questionable
• George Kittle – questionable 
• Fred Warner – questionable
• Talanoa Hufanga – questionable
• Jordan Elliott – questionable 
• Kyle Juszczyk – questionable 
• Jacob Cowing – questionable 

Cardinals vs. 49ers Key Players to Watch

Arizona Cardinals

James Conner: Arizona’s offense wasn’t great in Week 4, but Conner had a big game, rushing for 104 yards and a score on 18 carries. With Arizona likely trying to keep the 49ers offense off the field, Conner could see a major workload in Week 5. 

San Francisco 49ers

Deebo Samuel: After missing one week with a calf strain, Samuel returned against the Patriots, catching three passes for 58 yards and adding a pair of carries for 14 yards. He should be relied on heavily with Christian McCaffrey (Achilles) still out. 

Cardinals vs. 49ers Prediction and Pick

This game has OVER written all over it. 

Both of these teams have hit the OVER in three of their four games this season, and Arizona has been one of the worst defenses in the NFL, allowing the fourth most points and sixth most yards per play in the 2024 season.

San Francisco ranks third in the league in yards per play and is top 10 in scoring, so it should dominate this Arizona defense that gave up 42 points to Washington in Week 4. 

In four games this season, the Cardinals have cleared 50 combined points three times, and the 49ers have done so twice, including one game at home. 

I expect both offenses to thrive – especially San Francisco’s – in Week 5. 

Pick: OVER 49.5 (-112)

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Odds refresh periodically and are subject to change.

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