Arizona Cardinals vs New Orleans Saints Prediction, Odds and Picks for Sunday, 09/07/25

The NFL season has finally returned and with it comes a number of exciting matchups across the football landscape in Week 1. While there are plenty of games to look forward to, one under-the-radar contest that has caught my eye comes in New Orleans between the Cardinals and Saints. Arizona enters this season with increased expectations following a middling campaign a season ago, and the Cardinals will have the perfect opportunity to start off on the right foot against a Saints team that should be one of the worst teams in football this season.

New Orleans is finally finished with the Dennis Allen era, but the Saints are still in a very difficult spot in 2025. Kellen Moore steps in as the new head coach to try and revive an offense that was really struggling down the stretch a season ago, but even with a surprising amount of talent on that side of the ball, the Saints are still going to be leaning on Spencer Rattler at quarterback. Frankly, that’s a losing proposition and not one that I anticipate working for New Orleans in what obviously feels like a hard reset following years of salary cap manipulation and operating on the fringes of contention in the NFC.

As for Arizona, the Cardinals are a team that I’m cautiously optimistic about this season. After all, this is a team with all of the tools to be successful on offense, and I’m interested in what head coach Jonathan Gannon has planned for his continued reshaping of a defense that was one of the worst in football a couple of years ago. While that turnaround still might be a year away, I’m confident in Arizona’s ability to take care of arguably the worst team in the NFL in Week 1, so let’s back the Cardinals to win and cover the current number.

Cardinals vs Saints prediction: Cardinals -6.5 (-105) available at time of publishing. Playable at that number. 

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Even though I’m high on this Cardinals team from a long-term perspective this season, I am pretty skeptical of Arizona’s defense this season. After all, the Cardinals was 29th in EPA per play on defense a season ago and ranked near the bottom of the league in points per game allowed. The Saints’ offense still has some real talent around Rattler, and he should be able to lead New Orleans to at least 17 points in this game. On the other side, the Cardinals’ offense is a high-flying unit with playmakers all over the field and they should see success throughout against one of the worst defenses in football a year ago. All things considered, I’ll take the Over in the Big Easy.

Cardinals vs Saints prediction: Over 42.5 (-110) available at time of publishing. Playable to 43.5.

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