Buffalo Bills vs New Orleans Saints Picks and Predictions September 28th 2025

Buffalo Bills vs New Orleans Saints September 28th 2025

The New Orleans Saints travel to Highmark Stadium to take on the Buffalo Bills in Week 4 of the 2025 NFL season. This game kicks off at 1:00 PM on Sunday, September 28, and will be broadcast on CBS. The weather forecast predicts clear skies, making it a pleasant day for football in Orchard Park, NY.

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The Saints, led by head coach Kellen Moore, are looking to secure their first win of the season. They currently hold a 0-3 record. On the other hand, the Bills, coached by Sean McDermott, have started strong with a 3-0 record. Buffalo has performed well at home, winning both of their games at Highmark Stadium this season.

Saints vs Bills Key Information

• Sport: NFL
• Teams: New Orleans Saints vs. Buffalo Bills
• Venue: Highmark Stadium in Orchard Park, NY USA
• Date: Sunday, September 28, 2025
• Betting Odds: Saints Moneyline +940, Bills Moneyline -1708, Saints Spread +16.5 (-112), Bills Spread -16.5 (-109), Total Over 47.5 (-115), Total Under 47.5 (-105)

The Saints Can Win If…

The New Orleans Saints are looking to bounce back after a tough loss to the Seattle Seahawks, 44-13. Spencer Rattler threw for 218 yards with one touchdown and one interception. Tight end Jack Stoll caught a touchdown pass, while Chris Olave led the team with 57 receiving yards on ten catches.

Despite recent losses, the Saints have strengths that can lead to victory. They have a strong rushing attack, ranking 14th in the league last season. Alvin Kamara is a key player with 186 rushing yards this season, showing his ability to make plays on the ground.

The Saints’ defense also offers opportunities. They ranked 10th in sacks last season, with players like Carl Granderson contributing significantly. If they can pressure the opposing quarterback, it could turn the game in their favor.

The Bills Can Win If…

The Buffalo Bills are coming off a strong win against the Miami Dolphins, securing a 31-21 victory at Highmark Stadium. Josh Allen led the offense with 213 passing yards and 3 touchdowns. James Cook also made a significant impact with 108 rushing yards and a touchdown.

The Bills have been impressive on offense, ranking 2nd in scoring last season with 525 points. They also have a strong running game, ranking 9th in rushing yards. Their ability to convert on third downs, with a 44.1% success rate, shows their efficiency in keeping drives alive.

On defense, the Bills excel in forcing turnovers, ranking 4th in opponent passing interceptions last season. They also led the league in fumbles recovered, highlighting their knack for taking the ball away. Despite injuries, their depth and recent performances make them a formidable team to face.

The Lean

The Buffalo Bills are favored by 16.5 points against the New Orleans Saints. The Bills have an impressive record against the spread (ATS) at home, going 7-1 in their last eight games. Given the Bills’ strong offensive performance and the Saints’ struggles, the recommendation is to take the Bills -16.5. The model projects a score of Bills 35, Saints 17.

The total for the game is set at 47.5 points. The Saints have been hitting the over in 75% of their recent games as underdogs. The Bills also have a strong trend towards the over in home games, going 3-0 in their last three. The recommendation is to take the over 47.5. The model projects a total score of 52 points.

Bills vs Saints Preview

The Buffalo Bills (3-0) return from a bye chasing their 14th straight home win when they face the New Orleans Saints (0-3) in Orchard Park. Buffalo is averaging 34 points per game, fourth best in the league, and has yet to commit a turnover. Josh Allen leads an offense producing 420 yards per game, while the Saints continue to beat themselves with a league-high 31 penalties.

New Orleans has dropped three straight, including a 44-13 blowout loss in Seattle. Spencer Rattler and the Saints’ offense showed flashes in closer games against Arizona and San Francisco, but turnovers and penalties remain defining issues.

Injury Report

Buffalo held out right tackle Spencer Brown (calf), defensive tackle Ed Oliver (ankle), and linebacker Matt Milano (pectoral) in practice. Their absence would impact both protection and run defense.

The Saints may get help on the line as Trevor Penning returned to full practice after a preseason toe injury. But depth remains thin, with Dillon Radunz (toe) and Chase Young (calf) still sidelined.

Betting Results and Trends

The Bills opened as heavy home favorites on the NFL odds page. The spread climbed further after the Saints’ collapse in Seattle. Buffalo is 2-1 ATS and trending Over with high-scoring wins. New Orleans is 0-3 ATS with two Unders and one Over. Buffalo’s penalty discipline adds an edge against a Saints team that continues to stall drives with pre-snap mistakes.

What It Means Moving Forward

Buffalo enters another soft spot in the schedule as it builds toward AFC seeding. The defense still needs sharper third-down execution, but the offense’s balance has masked lapses. For New Orleans, this week is about survival. Avoiding an 0-4 hole is crucial, and playing clean football is the only way to stay competitive on the road.

ScoresAndStats Handicappers and Picks

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