San Francisco 49ers vs New Orleans Saints Prediction, Odds and Picks for Sunday, 09/14/25

It’s the start of the Mac Jones era in San Francisco as the 49ers travel to take on the New Orleans Saints in Week 2. Brock Purdy is out with turf toe, potentially for over a month, and the former Patriots first-round bust is taking the reins. Kyle Shanahan reportedly was infatuated with Jones in the run-up to his draft, and Shanahan will finally get the chance to coach him here. I’m not particularly bullish on Jones’ future, but I don’t think within this system he’s all that big of a downgrade from Purdy.

The 49ers were 7-point favorites for this game last week on the lookahead line, and that’s a pretty big move, especially with New Orleans having an uninspiring quarterback situation of their own. Spencer Rattler averaged 4.7 yards per attempt in a loss to the Cardinals last week, and it doesn’t look like last year’s 5th-round pick improved all that much this offseason. The 49ers covered the spread in a road win last week over the Seahawks, despite Purdy throwing 2 interceptions, because the rest of their team is still that good.

And it looks like the defense is going to get back to its formerly elite levels with Robert Saleh now back calling the defense for Shanahan like old times. San Francisco picked up that win on the road despite the fact that Christian McCaffrey couldn’t get going at all, averaging just 3.1 yards per carry. The final score looks close, but the 49ers outgained the Seahawks 384-230 in that one.

49ers vs Saints prediction: 49ers -3 (-115) available at time of publishing. Playable at that number.

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