New Orleans Saints vs Buffalo Bills Prediction, 9/28/2025 NFL Picks, Best Bets & Odds Week 4

Game: New Orleans Saints vs Buffalo Bills

Date: Sunday, September 28, 2025

Location: Highmark Stadium in Orchard Park, NY

TV: CBS

Odds-Point Spread: Bills (-16.5)

Total-Over-Under: 47.5

The New Orleans Saints (0-3) are traveling to Highmark Stadium on Sunday where they will attempt to defeat the Buffalo Bills (3-0). New Orleans opens as 16.5-point underdogs. The total has been set at 47.5.

The New Orleans Saints step onto the field holding a record of 0-3 on the year. The last time they stepped on the gridiron, the Saints took on the Seattle Seahawks and ended up losing by a score of 44-13. Alvin Kamara led the offense in rushing for the Saints with 18 carries for 42 yards (2.3 yds per attempt). Chris Olave left with an average of 5.7 yards per reception by earning 57 yards on 10 catches. Spencer Rattler went 28-39 with 218 yards through the air and 1 touchdown. He had a quarterback rating of 83.1 and ended the game with 1 pick. In the running game, the Saints gave up 87 yds on 33 attempts, which averages out to 2.6 yds per run allowed. New Orleans relinquished 16 completions on 21 tries for a total of 233 yards, and a completion rate of 76.2%. In all, they ran 68 plays which gave them a total of 284 yards. The New Orleans Saints ended up rushing 27 times and recorded 79 yards, which came out to an average of 2.9 yards per tote.

The Saints have tallied 906 total yards over the course of this year. New Orleans has tallied 36 first downs as a team, and they have been called for 31 infractions for 211 total yards. When examining getting in the endzone, New Orleans has attained 4 passing touchdowns and 1 rushing touchdown. They have turned the football over 2 different times (1 interception and 1 fumble). Offensively, they are sitting at 102.3 rushing yds which ranks them 18th in the league. If you look at getting in the endzone, the New Orleans Saints hold an average of 15.7 points per contest.

The Saints currently rank 25th in pro football when examining their defensive abilities, surrendering 30.0 points per game. They are allowing teams to run for an average of 3.6 yds per running attempt and 103.3 rushing yards per game over the course of this season. If you look at passing yards, the Saints have given up 630 total yards, ranking this team at 17th in pro football. They have given up 210.0 total yards per outing by way of the pass, and are giving up a completion rate of 70.8%. On the whole, they are giving up 313.3 yards per contest, which is 15th in the league. They have allowed 7 touchdowns through the air, and 2 touchdowns via the ground game. On the whole, they have surrendered 310 rushing yards through 3 outings on the year.

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The Bills head into this matchup 3-0 over the course of the season. In their last contest, the Bills got the win with a final of 31-21 against the Miami Dolphins. James Cook carried the rock 19 times for 108 yards, ending the contest with 5.7 yds per carry for Buffalo. Dalton Kincaid was the top contributor in the passing game for the Bills, snagging 5 footballs for 66 yds (13.2 yards per reception). Josh Allen (3 touchdowns) ended the game with 213 yds on 22-28 passing while his QB rating was 134.1. He didn't throw any interceptions and his avg yards per attempt was 7.6 yards. Buffalo gave up 25 running attempts for 130 yards (5.2 yards per rush). The Bills secondary conceded a completion percentage of 64.7%, relinquishing 146 yds on 22 out of 34 passing. The Bills finished the contest with a total of 360 yds while running 55 plays (6.5 yds per play). Buffalo rushed for 5.8 yds per carry, finishing the contest with 157 yards on 27 carries.

The Buffalo Bills maintain an average of 420.0 yards per game, which ranks them 1st in the league. They maintain an average of 163.0 rush yards per contest, and have toted the ball for 489 total yards. They have yet to turn the ball over. The Buffalo offense has surrendered 142 yds by way of 14 penalties, putting them 29th in the NFL if you look at helping out the opposition. In this campaign, the Bills have thrown for a total of 771 pass yds and are sitting at 257.0 pass yds per game, which ranks them 5th in the league. Regarding the points being put on the board, the Bills are ranked 4th in pro football, by tallying 34.0 PPG.

The Bills are giving up 23.7 points per contest, which has them sitting 20th in the league. They have surrendered 5 touchdowns by way of the pass in addition to 131.3 yards via the pass per outing, which has them sitting 2nd in the league. Buffalo has allowed a total of 468 rushing yards (156.0 total yards per game), as well as 4 touchdowns on the ground over the course of this season. The Bills defense has taken the field for 156 plays from the line of scrimmage, which ranks them at 1st in the NFL. The D has a total of 3 turnovers (2 forced fumbles and 1 interception) over the course of the season. On the whole, they have surrendered 71 pts.

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

Parlays Pundit's Pick: Take the Bills -16.5 and over 47.5 total points

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