The New Orleans Saints have a different look heading into this season, with a new head coach and changes in the quarterback room, but the same questions linger ahead of a Week 1 visit from the Arizona Cardinals.
While New Orleans is a team in transition as Kellen Moore takes the reins, Arizona has real playoff aspirations with Kyler Murray healthy to start the year, and my Cardinals vs Saints predictions expect the visitors to make some noise at Caesars Superdome.
Read on for my top NFL picks and an early breakdown of this Sunday, September 7, battle.
Cardinals vs Saints predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
Early Cardinals vs Saints spread pick: Cardinals -6.5 (-105)
The Arizona Cardinals’ slide during the second half of last season took the shine off a 6-3 start. Still, there are plenty of reasons for September optimism, particularly with an offense built around Kyler Murray, Marvin Harrison Jr., and Trey McBride.
That’s in stark contrast to a New Orleans Saints team that could challenge for the league’s worst record, so I’ll gladly lay the points when the spread is less than a touchdown.
The Cardinals were 11-6-1 ATS last year despite some struggles down the stretch, and they’ve got the speed to thrive indoors. But this pick is just as much about the uphill task facing the Saints in 2025. Spencer Rattler gets the nod as New Orleans’ QB to start the year, but he threw five interceptions across his seven outings last year, to go with a 57% completion rate.
Equally worrying, the Saints were 0-8 without Derek Carr last season, and seven of those losses came by more than this 6.5-point spread.
Even if Rattler shows improvement to kick off Year 2, the hosts may have a hard time unlocking Alvin Kamara and Chris Olave, given Arizona’s defensive line upgrades, which include Josh Sweat and Dalvin Tomlinson.
This looks like the strongest Cardinals roster since Jonathan Gannon’s arrival in 2023, and I’m expecting a bold statement from the visitors in this opening weekend clash.
Early Cardinals vs Saints total pick: Over 42.5 (-120)
Even factoring in early-season rust, this line feels too low. Arizona flew out of the traps last season, scoring 69 points across its first two games, and we could see similar production here against a New Orleans defense that allowed the third-most yards per game last year (379.9).
Of course, the Saints were even more lethal in those opening weeks when all their pass-catchers were healthy. They cashed this Over with their team total alone in Weeks 1 and 2.
Arizona's trends feel more meaningful. The visitors finished third in the NFL in EPA per play on first down in 2024, and the Murray-James Conner backfield is well placed to keep the Saints off-balance in the ground game. It would be a surprise if the Cards fell short of the 25-point mark on Sunday.
The numbers support the Over, which is 6-2 in the past eight meetings between these teams. It was also 4-1 in Arizona’s final five contests last season, including a 47-24 victory against the San Francisco 49ers in Week 18.
Both teams have explosive playmakers to spark quick-hitting drives, and while I’m picking the Cardinals defense to have the upper hand against Rattler, there’s still scope for Olave and speedster Rashid Shaheed to break free down the field and nudge the total closer to the Over.
Cardinals vs Saints odds
- Cardinals vs. Saints spread: Saints +6.5
- Cardinals vs. Saints moneyline: Cardinals -290, Saints +235
- Cardinals vs. Saints Over/Under: 42.5
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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