New Orleans Saints vs. Buffalo Bills Prediction and Picks - Sunday, September 28, 2025
Use Code SSWC The Bills can extend their perfect start this Sunday when Josh Allen and his teammates host New Orleans. For great side and total picks on this game, read on for our Saints vs. Bills prediction and picks. Kick-off is scheduled for 1:05pm PT (4:05pm ET) at Highmark Stadium, home of the Bills.
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Saints seek first win
The New Orleans Saints (0-3) have begun the 2025 season winless, with last week's reverse the most painful yet. The Saints were left shell-shocked by Seattle's quick start and trailed 38-3 towards the end of the second quarter, eventually tightening up to actually win the second half and limit the final score to 44-13. The low point for New Orleans came in the first quarter, where it scored three times in less than five and a half minutes, including a punt return TD fielded by Tory Holton on the Seahawks' five-yard line.
That blowout undid some of the goodwill garnered in the Saints' opening game, tight losses at home to Arizona and San Francisco. The focus will be on damage control in Buffalo this week, particularly against Allen's fearsome arm. The Saints are allowing opposing quarterbacks to complete 70.8% of pass attempts so far, the fourth-highest mark in the NFL, and have already given up seven TDs through the air in three games. Offensively, New Orleans has leaned heavily on second-year pro Spencer Rattler: the 24-year-old is averaging 213 passing yards/game so far in 2025 while throwing four TDs and a single INT. The next step for Rattler will be to improve on his mediocre 50% conversion in the red zone, which ranks 19th among NFL franchises this season.
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On the injury front, defensive end Chase Young (calf) and offensive lineman Dillon Radunz (toe) were sidelined on Thursday, while right tackle Taliese Fuaga participated fully and looks set to return to the team after being held out against the Seahawks.
Bills aim for four in a row
The Buffalo Bills (3-0) have surged out of the gate, apparently stung by last year's tough AFC Championship loss to the Chiefs and hell-bent on getting Josh Allen that elusive ring. An incredible come-from-behind win in Week 1 over the Ravens, who led by 15 points at one stage, was followed by rather more routine defeats of the Jets and Dolphins to open up an early two-game lead at the top of the AFC East. Against Miami Allen recorded his 200th passing touchdown and 300th overall touchdown, overtaking Patrick Mahomes as the fastest quarterback to reach that milestone - though he and the Bills will be disappointed to have struggled through much of the game on their way to a 31-21 win.
Going into Week 4, Allen has thrown 755 yards through the air (ranking eighth among NFL QBs) with five TDs and zero INTs. He is one of three quarterbacks to have thrown at least five TDs at this stage without allowing an interception, alongside Lamar Jackson and Baker Mayfield. He ranks fifth among NFL QBs with 114 rushing yards while getting over the line for two TDs. James Cook is also enjoying a spectacular start to the season, placing second in the NFL with 284 rushing yards while scoring four TDs - helping Buffalo put up the best numbers of any team on the ground so far with an average of 163 yds/game.
The Bills risk going into Sunday's game without three starters. Defensive tackle Ed Oliver (ankle), linebacker Matt Milano (pectoral) and right tackle Spencer Brown (calf) all sat out Wednesday and Thursday's practice and face an uphill battle to regain fitness in time.
Spread Pick for Saints vs. Bills
- Saints +16.5 (five units)
While the Bills are clearly the superior team here going into Sunday's game, covering more than two scores is a tall order and one I think will be beyond them, particularly with up to three starters missing the cut due to injury. The Saints got destroyed last time out in a freak loss to Seattle, but their two previous losses, both by a seven-point margin, are probably more indicative of where they are right now as a team, keeping both games relatively close.
Take the Saints.
Over/Under Pick for Broncos vs. Chargers
- Under 46.5 (five units)
The Bills are putting up big numbers in front of their own fans so far this year and I think that will continue against the Saints. Buffalo is 2-0 on the over playing at home with an average total of 76.5 points per game and went 10-4 in 2024 as the favorite. The Saints are 2-1 on the over so far in 2025
Take the over.
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