Cardinals vs. Saints Prediction, Odds, Spread, Injuries, Trends for NFL Week 1

The Cardinals are road favorites in Week 1.

Can the Arizona Cardinals and quarterback Kyler Murray cover in Week 1? / Joe Rondone/The Republic / USA TODAY NETWORK via Imagn Images

The Arizona Cardinals are going to be a popular pick to win their season opener in 2025, as they’re set as road favorites at the best betting sites against the New Orleans Saints.

The Saints have one of the lowest win total projections in the NFL this season, and they landed on quarterback Spencer Rattler (who was 0-6 in the 2025 season) as their starter over second-round pick Tyler Shough. 

There’s a lot of questions about the talent on this New Orleans roster, but new head coach Kellen Moore will look to shock some people in Week 1 at home.

Arizona, on the other hand, has playoff aspirations after a poor finish led to an 8-9 2024 season. The Cardinals have a chance in a pretty wide open NFC West to take home a division title, but they’ll need the best version of Kyler Murray for 17 games – not just the first few months – to get it done.

Let’s dive into this Week 1 matchup with the latest odds, trends, injury reports, players to watch and – of course – a prediction. 

Cardinals vs. Saints Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• Cardinals -6.5 (-110)
• Saints +6.5 (-110)

Moneyline 

• Cardinals: -285
• Saints: +230

Total

• 42.5 (Over -112/Under -108)

Cardinals vs. Saints How to Watch

• Date: Sunday, Sept. 7
• Time: 1:00 p.m. EST
• Venue: Caesars Superdome
• How to Watch (TV): CBS
• Cardinals record: 0-0
• Saints record: 0-0

Cardinals vs. Saints Betting Trends

• The Cardinals were 11-6 against the spread in 2024.
• The Saints were 7-10 against the spread in 2024.
• The OVER was 8-8-1 in the Cardinals’ games in 2024.
• The UNDER was 9-8 in the Saints’ games in 2024. 

Cardinals vs. Saints Injury Reports

Cardinals Injury Report

• Will Hernandez – questionable
• Dalvin Tomlinson – questionable

Saints Injury Report

• Trevor Penning – questionable

Cardinals vs. Saints Key Player to Watch

• Kyler Murray, Quarterback, Cardinals

Can Kyler Murray finally put together a complete season and lead the Cardinals to some playoff success? 

Murray has just one winning season as a starter and is 36-45-1 for his career entering the 2025 campaign. A disappointing December led to an 8-9 finish in 2024, but the Cardinals have a chance to win a wide open NFC West (especially with Matthew Stafford’s back injury) in 2025. 

After throwing for 21 touchdowns to 11 picks in 2024, Murray is looking to improve on that in 2025 and show that he is a franchise quarterback. 

Cardinals vs. Saints Prediction and Pick

Earlier this week, SI Betting’s NFL betting insider Iain MacMillan shared his pick for this game in his Road to 272 bets – where he bets on every game in the NFL season. 

MacMillan is riding with the Cardinals, and he called them a “no-brainer” bet with the spread inside seven points: 

The New Orleans Saints are projected to be the worst team in the NFL this season, and things didn't get better for them when they announced that Spencer Rattler has won the starting job at quarterback over their second second-round round draft pick, Tyler Shough. Rattler went 0-6 as a starter last season, completing just 57% of passes, including four touchdowns and five interceptions.

When it comes to the Arizona Cardinals, they've typically been a good bet in September. Kyler Murray regresses as the season progresses, but he can rely on his athleticism more in the early weeks, leading to Arizona being a tough opponent in the first month of action.

I agree with MacMillan, as New Orleans’ quarterback situation is impossible to trust in the 2025 season. 

Even though Arizona finished under .500 in 2024, it was still one of the best teams in the NFL against the spread (11-6). 

With Murray healthy, the Cardinals should be a playoff contender in the NFC, so they’ll need to show that against a bad Saints team. I’ll back them to run away with this game after watching how much the New Orleans offense struggled without Derek Carr in 2024. 

Pick: Cardinals -6.5 (-110 at DraftKings)

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Odds refresh periodically and are subject to change.

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