New Orleans Saints vs Buffalo Bills Picks and Predictions for Sunday, September 28, 2025

By: David Anicetti Updated 09/26/2025, 01:04 PM ET
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The New Orleans Saints visit the Buffalo Bills on Sunday at Highmark Stadium. Kickoff is at 1:00 PM ET on CBS. New Orleans is 0-3 after a 44-13 loss at Seattle and sits last in the NFC South. Buffalo is 3-0 after beating Miami 31-21 and is first in the AFC East. The Bills are favored by more than two touchdowns (-17) with the total at 47.5. Join a passionate community of fans who rely on our data-driven free NFL picks to secure their victories.

New Orleans Saints Preview

Quarterback Spencer Rattler has thrown for 639 yards with 4 touchdowns and just 1 interception. Rattler has relied on Alvin Kamara in the backfield, who has 186 rushing yards on 50 carries. Rattler spreads the ball to Juwan Johnson, who leads with 176 yards and a touchdown, and Chris Olave, who has 165 yards. Still, New Orleans has averaged only 15 points per game and has struggled to finish drives.

On defense, veteran Demario Davis leads with 31 tackles, and Carl Granderson has been the top pass rusher with 3.5 sacks. The problem has been giving up big plays, allowing 44 points to Seattle and 26 to San Francisco. Injuries up front have also limited the push against the run. The Saints need long possessions and better tackling to stay in this game.

Buffalo Bills Preview

Quarterback Josh Allen has been sharp with 755 passing yards and five touchdowns without a turnover. He has connected with Keon Coleman for 158 yards and a score, while tight end Dalton Kincaid has 151 yards and 2 touchdowns. James Cook leads the rushing attack with 284 yards and 4 touchdowns, giving Buffalo steady production on the ground.

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Defensively, the Bills have dealt with injuries to Matt Milano and Ed Oliver, but continue to find answers. Terrel Bernard has an interception, and Greg Rousseau and Joey Bosa bring pressure on the edge. Buffalo has held Miami and the Jets to a combined 31 points in two games, showing strength against the run and in the secondary.

New Orleans Saints vs Buffalo Bills Prediction

Buffalo has the stronger roster, the more consistent quarterback, and home-field advantage. Allen and Cook should put up points early, while the defense will limit New Orleans to short gains. The Saints have not shown enough offense to keep pace, especially on the road. Final Score Prediction: Buffalo Bills win 31-17.

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Best Picks

  • Buffalo Bills -17
  • Over 47.5
  • James Cook anytime touchdown
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