Arizona Cardinals vs. San Francisco 49ers Preview: Prediction, Best Bets, Odds, Depth Charts (10/1/23)

The undefeated San Francisco 49ers host the 1-2 Arizona Cardinals in a 4:25pm ET game this Sunday (10/1/23) in week 4 of the 2023 NFL season. The Cardinals are looking to make it back-to-back weeks with an upset victory as a double-digit underdog.

The 49ers are heavy betting favorites at -14 on the spread, while the over/under is set at 44 points. This article provides Cardinals vs. 49ers analysis, predictions and betting recommendations and explains why the best bet in this matchup is the over on 44 points.

Cardinals vs. 49ers Prediction & Best Bet

After the Cardinals upset the Cowboys last week, the 49ers now look like the best team in the NFC after 3 weeks. Can the surprisingly feisty Cardinals knock off another NFC contender?

Probably not, but it would not be surprising at all if they managed to cover the massive 14-point spread. Divisional games like this one tend to be closer than expected. The 49ers failed to cover as -7.5 favorites at the Rams, another divisional opponent, in week 2. But that wasn’t the case in these teams’ two games last season, which the 49ers won by 25 and 28 points.

While the Cardinals have looked much better than expected after three 3 weeks, we don’t yet have enough confidence in them to bet on them covering against San Francisco, even with such a massive spread. However, they have shown enough to be reticent about laying the points too, so we are staying away from betting the spread in this game.

Betting on the total looks much more appealing in this matchup. San Francisco has scored exactly 30 points in all three of its games so far this season as the offense has been humming with Brock Purdy back under center. They are 3rd in the league in scoring, 4th in total offense, and 2nd in EPA per play.

Arizona’s defense is unlikely to put up much resistance. Their defense is already weak on paper and they could be missing multiple starters this week including star safety Budda Baker, who is on IR. They have done a good job so far at keeping points off the board, allowing 22.3 per game (15th). However, they are 26th in yards allowed (367.7) and 22nd in EPA per play allowed.

San Francisco scored 38 points against Arizona in both of their games last year, and if they can at least match their current average of 30 points per game then the Cardinals would just need to score 14 points for the over to hit. That will not be easy against a 49ers defense that is top 5 in points, yards and EPA per play allowed. But the same was true against the Cowboys last week when Arizona scored 28 points.

The Cardinals’ offense has looked much better than expected with Josh Dobbs under center. They are 13th in scoring and 10th in EPA per play so far this season and have faced one elite defense (Dallas) and one solid one (Washington) on the road. Dobbs is protecting the football (0 interceptions, 2 fumbles lost), getting rid of it quickly (10th in time to throw at 2.51 seconds) and completing passes at a high rate (4th at 72% completions and 8th in CPOE at +5.2%).

Whether it’s the Cardinals scoring at least 2 touchdowns or the 49ers scoring over 30 points, there are multiple potential scenarios where the total goes over 44, which is why that’s the best bet in this game. The biggest concern with betting the over is a couple of injuries on both offenses, especially the Cardinals’ Marquise Brown and the 49ers’ Deebo Samuel, so keep an eye on their statuses before placing this bet.

Cardinals vs. 49ers Prediction & Best Bet: 49ers win 31-16, over 44 total points

Cardinals vs. 49ers Betting Odds


Oct. 01, 3:25 PM




Arizona Cardinals


San Francisco 49ers


Odds updated October 1st, 2023, at 6:14 pm

The spread in this game is sitting right at the key number of 14 and has hardly moved from that number since it opened. Even a 0.5-point shift in either direction would be significant, so keep an eye on that and try to get it at -13.5 if you want to bet on the 49ers or +14.5 if you want to bet on the Cardinals.

There has been more movement on the total, which opened at 42 and has been juiced up to 44 or 44.5 at different sportsbooks. Based on public betting trends, it’s unlikely to get much higher than that.

The implied outcome of these odds is the 49ers winning 29-15.

Cardinals vs. 49ers Key Injuries

Top WR Marquise Brown and backup RB Keaontay Ingram both popped up on the Cardinals’ injury report Thursday. Those are the only Cardinals injuries to monitor on offense, but the defense has several players to worry about. They are already missing starting S Budda Baker and LB L.J Collier, and now they could be without DT Jonathan Ledbetter and LBs Josh Woods and Krys Barnes.

All three of the 49ers’ starting wide receivers are on the injury report, but it’s a good sign that Brandon Aiyuk practiced (on a limited basis) Wednesday and Thursday after missing the last game. Deebo Samuel (ribs/knee) and Jauan Jennings (shin) missed those practices and their status, especially Deebo’s, is worth monitoring. On defense the only starter at risk of missing the game is LB Dre Greenlaw (ankle), who would be a big loss if he can’t go.

Cardinals vs. 49ers Key Matchups

Check out the key matchups and mismatches for Cardinals vs. 49ers below.

Cardinals’ offensive line vs. 49ers’ pass rush

A big part of the reason for the success of the Cardinals offense so far this season has been their pass protection. Dobbs has been under pressure on just 33% of his dropbacks, which is above average for all quarterbacks so far this season (14th). Dobbs has also been cool under pressure and leads all quarterbacks with 70.8% completions when under pressure.

That said, Arizona has not faced a pass rush as relentless as San Francisco’s (and that includes Dallas). The 49ers lead the league with 41 QB pressures and are 8th with a 27.9% pressure rate. They are also PFF’s highest-graded pass rush unit.

If Nick Bosa, Javon Hargrave and the rest of the 49ers’ front seven can get more pressure on Dobbs than he’s experienced so far this season, then the Cardinals’ offense may struggle more than they have in their first three games. That would make the over a riskier bet.

Cardinals Depth Chart

QB: Joshua Dobbs
RB1: James Conner
RB2: Keoantay Ingram
LWR: Marquise Brown
RWR: Michael Wilson
SWR: Rondale Moore
TE1: Zach Ertz

49ers Depth Chart

QB: Brock Purdy
RB1: Christian McCaffrey
RB2: Elijah Mitchell
LWR: Brandon Aiyuk
RWR: Deebo Samuel
SWR: Jauan Jennings
TE1: George Kittle

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Noah hails from Philadelphia and is a diehard Philly sports fan. He graduated from Penn where he was a sports writer and editor for the student newspaper and also spent a summer covering the Baltimore Orioles for He has been playing fantasy sports since before live stats were a thing, and he has enjoyed learning the nuances of DFS in recent years. As a current resident of Florida, he is hoping the wave of sports betting legalization will eventually reach his home state.

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