San Francisco 49ers vs New Orleans Saints Prediction, 9/14/2025 NFL Picks, Best Bets & Odds Week 2

Game: San Francisco 49ers vs New Orleans Saints

Date: Sunday, September 14, 2025

Location: Caesars Superdome in New Orleans, LA

TV: FOX

Odds-Point Spread: Saints (+4.5)

Total-Over-Under: 42.5

Caesars Superdome is the site where the New Orleans Saints (0-1) will try to defeat the San Francisco 49ers (1-0) on Sunday. San Francisco opens this contest as 4.5-point favorites from oddsmakers. The total comes in at 42.5.

The San Francisco 49ers step onto the field holding a record of 1-0 for this campaign. The last time they stepped on the gridiron, the 49ers took the field against the Seattle Seahawks and took home the win by a score of 17-13. Brock Purdy finished 26-35 with 277 yards passing and 2 TDs. He had a quarterback rating of 92.2 and ended the contest with 2 picks. Christian McCaffrey led the offense in rushing for the 49ers with 22 carries for 69 yards (3.1 yards per attempt). Christian McCaffrey averaged 8.1 yds per catch by tallying 73 yards on 9 catches. The San Francisco 49ers ran the football 36 different times and accrued 119 yards, earning them an average of 3.3 yds per carry. Overall, they ran 71 plays which totaled 384 yards. San Francisco surrendered 16 completions on 23 attempts for 146 yds, and a completion rate of 69.6%. When it came to stopping the run, the 49ers gave up 84 yds on 26 tries, which calculates to 3.2 yds per run allowed.

The 49ers have racked up 384 yds on the year. San Francisco has accumulated 15 first downs, and they have been hurt by 9 infractions for 61 yards. If you look at putting the ball in the endzone, San Francisco has tallied 2 passing touchdowns and 0 touchdowns on the ground. They have turned the ball over 2 different times. As a team, they're holding an average of 119.0 rush yds which has them ranking 12th in the league. Concerning getting in the endzone, the group from San Francisco hold an average of 17.0 points per contest.

Concerning passing yards, the 49ers have surrendered 146 yards, ranking them 8th in football. They are yielding a completion% of 69.6%. They have granted 1 touchdown on the ground. On the whole, they are conceding 230.0 yds per game, putting them 4th in pro football. They are giving up an average of 3.2 yds per running attempt and 84.0 rushing yds per contest on the year. The 49ers are ranking 9th in pro football when analyzing their defensive abilities, yielding 13.0 points per game.

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The Saints come into this game with a record of 0-1 over the course of the season. The last time they stepped on the gridiron, the Saints took a defeat with a final score of 20-13 when they faced the Arizona Cardinals. Alvin Kamara carried the rock 11 times for 45 yards, ending the contest with 4.1 yds per attempt for New Orleans. Juwan Johnson was one of the featured targets for the Saints, snagging 8 balls for 76 yds (9.5 yds per reception). Spencer Rattler walked away from the game with 214 yds on 27-46 through the air while his QB rating was 70.4. He didn't throw any picks and his average yds per pass attempt was 4.7 yds. New Orleans surrendered 27 running attempts for 146 yds (5.4 yards per rush). The Saints pass defense allowed a completion percentage of 72.4%, relinquishing 130 yards on 21 out of 29 through the air. The Saints finished the game with 315 yards and they ran 68 plays (4.6 yds per play). New Orleans rushed for 4.9 yards per attempt, finishing the game with 107 yds on 22 carries.

When examining the points being put on the board, the Saints currently sit 24th in the league, with an average of 13.0 points per game. For the season, the Saints have racked up 208 pass yards which has them sitting 14th in the league. They have carried the football for 107 total yards. The New Orleans Saints average 315.0 yards per contest, which is 16th in professional football. The New Orleans offense has yielded 89 total yards by way of 13 penalties, ranking them 1st in pro football when analyzing making mistakes.

They have surrendered 2 touchdowns via the pass plus 130.0 passing yds per game, putting them 3rd in pro football. New Orleans has surrendered a total of 146 rushing yds. Their defense has yet to take the ball away. The Saints defense has been on the field for 61 plays from scrimmage, which ranks them 15th in the NFL. The Saints are conceding 20.0 points per contest, ranking them 15th in football.

Who will win tonight's 49ers-Saints NFL game against the spread?

Tony's Pick: Take the 49ers -4.5

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