San Francisco 49ers vs New Orleans Saints Picks and Predictions for Sunday, September 14, 2025

By: Cameron Ross Published 09/08/2025, 11:40 PM ET

49ers vs Saints Game Info

The San Francisco 49ers will be on the road again this week with a game in New Orleans at the Caesars Superdome in Louisiana for a matchup at 1:00 PM against the New Orleans Saints. San Francisco comes into Week 2 undefeated on the year following a four-point road victory against the Seattle Seahawks to start the season. The New Orleans Saints stay at home this week, winless thus far this season, following a 7-point home loss to Arizona in week one. San Francisco is currently a 4.5-point favorite, and the total is set at 40.5. Stay in the news with our NFL Picks.

San Francisco 49ers Preview

Mr. Irrelevant Brock Purdy started the season strong for San Francisco, completing 26 passes for 277 yards and two scores to go along with 17 yards on five carries. Christian McCaffrey led the way out of the backfield with 22 carries for 69 yards. Ricky Persall Fit in nicely in the San Francisco offense in week 1, leading the team with 108 yards on 4 receptions. Tight end George Kittle chipped in heavily with 25 yards and one score on three grabs, while Jake Tonges added three catches for 15 yards and one touchdown.

New Orleans Saints Preview

Spencer Rattler was shaky during week 1, completing 27 of 46 passes for 214 yards and ran the ball four times for 29 yards in the game. Alvin Kamara led the team with 45 yards and one touchdown on 11 carries. Juwan Johnson proved to be the top target for New Orleans in week one with 76 yards on 8 receptions. Chris Olave added seven catches for 55 yards in the game.

San Francisco 49ers vs New Orleans Saints Prediction

The 49ers are the better team in this game, and their week 1 win will carry momentum into this matchup. Take the 49ers to overwhelm a below-average Saints team for 60 minutes this week. The depth and talent of the Niners will be the difference, leading to the road win and cover. Final Score Prediction, San Francisco 49ers win and cover 27-10.

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