A banged-up San Francisco 49ers squad will look to pick up a second straight road win as they visit the New Orleans Saints on Sunday afternoon.
My 49ers vs. Saints predictions believe that even this diminished version of San Francisco should have more than enough to handle New Orleans' Spencer Ratter-led offense.
Let’s break down this Week 3 matchup with my free NFL picks for September 14.
49ers vs Saints prediction
49ers vs Saints Best bet: 49ers -3 (-115)
The San Francisco 49ers saw two of their key offensive weapons go down to injury in Week 1. Both Brock Purdy and George Kittle are likely to be out for multiple weeks, with Kittle landing on IR with a bad hamstring.
That leaves San Francisco turning to backup quarterback Mac Jones in Week 2 against the New Orleans Saints. I’m not about to pretend that Jones has been particularly successful throughout his NFL career, but he at least has a positive touchdown-to-interception ratio and completes 65.9% of his passes.
That compares well to Spencer Rattler, who has yet to win an NFL game as a starter, has more interceptions than touchdowns, and completes only 57.3% of his passes. Rattler had a few good moments last week against the Cardinals, but he still didn’t do much, leading the Saints to just 13 points.
Jones is still the superior quarterback in this matchup, and he has Christian McCaffrey to rely on.
McCaffrey compiled 142 yards of offense alone in Week 1, and a similar performance alone might be too much for the Saints to contend with.
New Orleans just doesn’t have the weapons offensively to stay in this game, which is why I’m taking the 49ers to cover.
49ers vs Saints same-game parlay
I like San Francisco to win this game without too much trouble, but I’m not expecting a ton of offense from either team, which is why I like the Under.
McCaffrey is the most reliable offensive performer on the field by a mile, however, so I’m taking him to rack up yardage and pick up a score before all is set and done.
49ers vs Saints SGP
- 49ers -3
- Under 40.5
- Christian McCaffrey Over 121.5 rushing + receiving yards
- Christian McCaffrey anytime TD
Our big-ticket SGP: Onward, Christian soldier
- We can load up on McCaffrey prop picks as he should be the clear primary weapon for the 49ers, and represents a safe option for Jones to pass the ball to out of the backfield.
- Even in a game where he showed some promise, Rattler failed to throw a touchdown pass last week, and he’ll have a tough time finding the end zone against a capable 49ers defense.
49ers vs Saints SGP
- 49ers -3
- Under 40.5
- Christian McCaffrey Over 121.5 rushing + receiving yards
- Christian McCaffrey anytime TD scorer
- Christian McCaffrey Over 4.5 receptions
- Spencer Rattler Under 0.5 passing TDs
49ers vs Saints odds
- Spread: 49ers -3 | Saints +3
- Moneyline: 49ers -166 | Saints +140
- Over/Under: Over 40.5 | Under 40.5
More NFL picks and odds from Covers
49ers vs Saints trend to know
The Saints are 0-7 straight-up and 1-6 ATS in games started by Spencer Rattler. Find more NFL betting trends for 49ers vs. Saints.
How to watch 49ers vs Saints
| Location | Caesars Superdome, New Orleans, LA |
| Date | Sunday, September 14, 2025 |
| Kickoff | 1:00 p.m. ET |
| TV | FOX |
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