The San Francisco 49ers will look to get off to a 2-0 start when they visit the New Orleans Saints in a Week 2 matchup.
Based on what we saw in Week 1, I’m predicting a low-scoring game that will tilt San Francisco’s way.
Read on to see my early 49ers vs. Saints predictions and free NFL picks for Sunday, September 14.
49ers 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 49ers vs Saints spread pick: 49ers -6.5
While neither team looked incredible in Week 1, the San Francisco 49ers were able to rally for a 17-13 win over the Seahawks. Meanwhile, the New Orleans Saints never really found anything on offense in a 20-13 loss to the Cardinals.
In some ways, the two performances mirrored each other. Both San Francisco and New Orleans played well on defense but went long stretches without generating much of anything on offense. But I have much more faith in the 49ers to score when they need to.
Saints fans have the right to feel cautiously optimistic about Spencer Rattler, but he still only went 27-for-46 and 214 yards with no touchdowns. Alvin Kamara remains the most dynamic option for New Orleans, scoring their only touchdown, yet even he only compiled 57 yards of offense.
San Francisco would love to see more consistency out of Brock Purdy, but at least he’s shown he can produce offense in big spots, and Christian McCaffrey looked like his old self on Sunday, especially in the passing game.
I like the 49ers to cover here, though I’d pay to get the line below seven points if it moves further in San Francisco’s direction during the week.
Early 49ers vs Saints total pick: Under 43.5
One thing we can say for sure about both teams is that they showed up strong defensively in Week 1. The 49ers held Seattle to just 4.6 yards per play, while the Saints kept Arizona to an average of 4.5 yards.
Both teams were highly effective against the passing game. New Orleans as able to record five sacks and allowed 130 yards through the air, with San Francisco allowing only 146 passing yards.
On the other hand, both sides have some questions regarding offensive production.
Rattler had some good moments for the Saints on Sunday, though he wasn’t terribly efficient and failed to put the ball in the end zone all game long. McCaffrey continues to be a yardage machine for the 49ers, getting 142 yards on 31 touches, but Purdy turned the ball over twice before leading a game-winning drive in the final minutes.
These teams both hit the Under easily in Week 1, and points will be at a premium again in their Week 2 matchup. I expect the defenses to dominate here, with the Saints finding it especially difficult to break through. I like the Under unless the total drops dramatically late in the week.
49ers vs Saints odds
- 49ers vs. Saints spread: Saints +6.5
- 49ers vs. Saints moneyline: 49ers -290, Saints +235
- 49ers vs. Saints Over/Under: 43.5
How to watch 49ers vs Saints
- 49ers vs. Saints matchup
- Date: Sunday, September 14, 2025, 1:00 p.m. ET
- City: New Orleans, LA
- Venue: Caesars Superdome
- TV: FOX
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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