Cardinals vs. 49ers prediction, odds, spread, injuries, trends for NFL Week 4

Can the 49ers cover a double-digit spread for the second straight week?

San Francisco 49ers running back Christian McCaffrey.
San Francisco 49ers running back Christian McCaffrey. / Cary Edmondson-USA TODAY Sports

The San Francisco 49ers are the favorites to win the Super Bowl through the first three weeks of the 2023 NFL season, and they find themselves favored by two touchdowns in Week 4 against the Arizona Cardinals. 

Arizona is undefeated against the spread, but the team has won just one game – an upset of the Dallas Cowboys last week – in 2023. The Cardinals were expected to be one of the worst teams in the league this season, but they have actually been within one possession or won every game they’ve played. 

Does that spell trouble for Brock Purdy and company? 

The 49ers have 10 days off coming into this game after winning on Thursday Night Football in Week 3, which should be a good sign for Deebo Samuel and Brandon Aiyuk getting healthy for this Week 4 matchup. 

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Cardinals vs. 49ers odds, spread and total in NFL Week 4

Cardinals vs. 49ers betting trends

  • The Cardinals are 3-0 against the spread this season.
  • The 49ers are 2-1 against the spread this season.
  • The OVER is 2-1 in the Cardinals’ three games.
  • The UNDER is 2-1 in the 49ers’ three games. 

Cardinals vs. 49ers injury reports

Arizona Cardinals injury report

  • Josh Woods – questionable
  • Zaven Collins – questionable
  • Krys Barnes – questionable

San Francisco 49ers injury report

  • Dre Greenlaw – questionable
  • Brandon Aiyuk – questionable
  • Ambry Thomas – questionable
  • Deebo Samuel – questionable

Cardinals vs. 49ers how to watch

  • Date: Sunday, Oct. 1
  • Game Time: 4:25 p.m. EST
  • Venue: Levi’s Stadium
  • How to Watch (TV): FOX
  • Arizona Cardinals Record: 1-2
  • San Francisco 49ers Record: 3-0

Cardinals vs. 49ers key players to watch

Arizona Cardinals

James Conner: If Arizona is going to keep this game close, it’s going to need to lean on James Conner, who has been terrific in 2023. The veteran running back is averaging 5.2 yards per carry and has scored twice already this season. He had 14 carries for 98 yards in the upset win over Dallas. 

San Francisco 49ers

Christian McCaffrey: Speaking of good running backs, CMC may be the best in the league, and he’s certainly shown it this season for the 49ers. The former Carolina Panther has 353 rushing yards (leads the NFL), 70 receiving yards and three scores in three weeks.  

Cardinals vs. 49ers prediction and pick

Even though Arizona has been great against the spread this season, I think the 49ers can win this game in a big way. 

San Francisco has already blown out the New York Giants (who beat Arizona by three) and the Pittsburgh Steelers this season, and the team is in the top four in yards per play on offense and top three in yards per play allowed on defense. 

I think San Francisco’s pass rush will wreak havoc on Josh Dobbs, and the team is equipped to slow down Conner as well – allowing just 3.7 yards per carry in 2023. 

It’s a lot to ask a team to cover by this much in a game, but the 49ers weren’t at full strength in Week 3 and did so against a better Giants team. 

With 10 days off to prepare, they should roll against the Cards. 

Game odds refresh periodically and are subject to change.

Find Peter Dewey's betting record here.