Bookmakers have a beefy spread for Week 4’s non-conference clash between the New Orleans Saints and Buffalo Bills.
Oddsmakers are asking Buffalo backers to swallow a ton of chalk with this first-vs-worst matchup on Sunday.
Here are my early Saints vs. Bills predictions and NFL picks for this September 28 clash.
Saints vs Bills predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
Early Saints vs Bills spread pick: Saints +16.5
We know the Buffalo Bills are great and the New Orleans Saints ain’t... but this is a monster spread for this point in the schedule.
That’s not saying Buffalo can’t blow this point spread out of the water, but I am hesitant to lay this lumber. The Bills could jump out to a big lead and put the bus on cruise control in the second half, as they protect what has already been an injury-prone roster.
New Orleans had a rough day in Seattle in Week 3. A blocked punt set up the Seahawks for an easy TD, and Seattle also returned a punt 95 yards for a score. The Saints couldn’t stay out of their own way, with 11 penalties for 77 yards against.
The look-ahead line for this game was Bills -12.5 before the start of the season, and even a Buffalo -14 would be reasonable in my eyes. This line had already climbed to -17 at some books and it will likely go higher before anyone shows interest in NOLA.
My early lean is to take all those points with the Saints, but I’d wait and see just how high that number goes before getting involved.
Early Saints vs Bills total pick: Under 48.5
If the Bills are going to cover this sizable spread, they’re going to need a butt-ton of points. The total is at 48.5 points, and I’m leaning Under.
Game script says the Bills are protecting a big lead in the second half, which means a slower tempo and more handoffs to kill the clock. If the scoreboard is as lopsided as oddsmakers project, Josh Allen may take a seat before the final whistle blows.
New Orleans' offense is among the least explosive in the NFL, with only four passing plays of 20 yards or more and an average of 4.4 yards per play. The Saints know they can’t win a shootout against Buffalo, so we could see a noticeable swing in pace for this offense.
Through three weeks, NOLA is playing one of the more up-tempo attacks in the league. It’s tied with Buffalo (and Dallas) for the most plays per game (68.7) and runs no-huddle at the second-highest rate (26.9%). Going fast against the Bills might not be the best approach.
There have been 30 regular-season games with a spread of -16.5 or higher since 2015, and those contests have produced a 12-18 Over/Under count (60% Unders)
Saints vs Bills odds
- Saints vs. Bills spread: Bills -16.5
- Saints vs. Bills moneyline: Saints +980, Bills -1800
- Saints vs. Bills Over/Under: 48.5
How to watch Saints vs Bills
- Saints vs. Bills matchup
- Date: Sunday, September 28, 2025, 1:00 p.m. ET
- City: Orchard Park
- Venue: Highmark Stadium
- TV: CBS
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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