San Francisco 49ers vs New Orleans Saints Prediction 9/14/2025 Today’s NFL Picks

The San Francisco 49ers and the New Orleans Saints meet Sunday in NFL action from Caesars Superdome. Here’s a 49ers vs Saints prediction. We will look at this from a betting perspective and determine the best 49ers vs Saints pick. We will examine:

The San Francisco 49ers recent form and player performance

The New Orleans Saints recent form and player performance

Recent betting trends and streaks involving the San Francisco 49ers

Recent betting trends and streaks involving the New Orleans Saints

Recent betting trends in games played between the 49ers and Saints

A summary that ties it all together and produces a favorable betting outcome for the 49ers vs Saints game

San Francisco 49ers Betting Preview

For what it’s worth, San Francisco had a pretty solid preseason overall—outside of their opener, anyway. The Niners lost that one to the Denver Broncos 30-9 but then bounced back with a win over the Raiders 22-19 in game two. In the exhibition finale versus the Los Angeles Chargers on August 23, the 49ers scored 24 points in the second half on the way to a 30-23 victory. QB Tanner Mordecai did most of the passing work, going 10-of-13 for 103 yards and a score. Jeff Wilson rushed for 41 yards and a score on 11 totes, and Malik Turner led the receivers with his three catches for 41 yards total.

In their regular-season debut this year, the 49ers took on the Seattle Seahawks. San Francisco went into the fourth quarter trailing by a field goal then scored 10 more points to power out a 17-13 comeback victory. QB Brock Purdy had an up-and-down day with 277 yards, two TDs and two picks on 26-of-35 passing. Leading rusher Christian McCaffrey carried 22 times for a nice 69 yards, while Ricky Pearsall led the receivers with his four catches for 108 yards. McCaffrey added nine catches for 73 yards as well.

New Orleans Saints Betting Preview

Over on the New Orleans side, they kicked off their preseason with a matchup versus the Los Angeles Chargers, eventually taking the loss 27-13. The Saints looked better in game two versus the Jacksonville Jaguars, managing to pull off a 17-17 tie. Game three was another loss however, this time 28-19 versus the Denver Broncos to give the Saints an 0-2-1 exhibition record. In the loss to Denver, New Orleans’ Tyler Shough threw for 102 yards on 12-of-20 passing but also had a rush touchdown. Devin Neal led the ground attack with five carries for a tepid 20 yards, and lead receiver Kevin Austin pulled in three passes for 34 yards.

In Week 1 versus the Arizona Cardinals, the Saints were within a touchdown 17-10 by halftime. New Orleans held the Cards to a field goal in the second—but mustered only a field goal themselves—in a 20-13 loss. Spencer Rattler threw for 214 yards on a 27-of-46 line, and Alvin Kamara carried 11 times for 45 yards and a score. Juwan Johnson had eight catches for 76 yards to top the receivers in the defeat.

Why the New Orleans Saints will win

The 49ers have lost six of their last seven games as favorites following a win.
Justin Reid’s team has won each of its last three games with him playing against Brandon Aiyuk.
The 49ers have failed to cover the spread in each of their last 10 games as favorites following a win.
The underdogs have covered the spread in four of the 49ers’ last five games at Caesars Superdome.
The 49ers have lost the first quarter in eight of their last 10 Week 2 road games against NFC opponents.
The home team has won the first half in each of the 49ers’ last four games.

Why the San Francisco 49ers will win

The favorites have won each of the Saints’ last seven games.
The Saints have lost each of their last four home games.
The Saints have failed to cover the spread in each of their last five games as underdogs against NFC West opponents.
The 49ers have covered the spread in five of their last six games as road favorites following a Division game.
The Saints have lost the first quarter in four of their last five games against NFC West opponents.
The Saints have lost the first half in four of their last five games.

Total Points Facts

Each of the 49ers’ last six games as favorites following a win have gone UNDER the total points line.
Each of the Saints’ last four home games have gone UNDER the total points line.

49ers vs Saints Prediction

I’m going to stay with the Niners. San Francisco pulled off a gritty road win over Seattle in their opener, but there are a few mistakes to correct before moving on. The offense wasn’t too bad in that one with 384 total yards (265 passing) and 24 first downs. The two interceptions didn’t help though, nor did the nine penalties for 61 yards. That said, San Francisco’s D did a nice job, holding the Seahawks to just 230 yards (140 passing), 14 first downs and 3-of-10 on third-down tries alongside a couple of fumble recoveries. That unit should be able to keep the Saints in check during this weekend’s matchup, and I like the 49ers to control things the whole way.