The New Orleans Saints’ season has unraveled quickly. At 0-3, they’re staring down a brutal Week 4 matchup against the undefeated Buffalo Bills. The latter have looked every bit like one of the AFC’s premier teams. New Orleans needs any sort of spark to prove they can compete. At the same time, Buffalo has to avoid falling into the dreaded trap of overlooking this game. As Highmark Stadium braces for this lopsided contest, the stage is set for some bold predictions that could define whether this game is simply another Bills blowout or something more competitive than expected.
Previewing Saints vs. Bills
The Saints (0-3) head to Highmark Stadium in Orchard Park for a daunting Week 4 matchup against the Bills (3-0). The contrast between the two sides is stark. Buffalo has surged to an unbeaten start behind Josh Allen’s steady leadership and a defense that has suffocated opponents. Meanwhile, New Orleans arrives on the heels of an embarrassing Week 3 loss to Seattle. The Saints are still searching for offensive rhythm and stability at quarterback.
Pundits have little faith in a Saints upset, with Buffalo favored by double-digits. New Orleans hasn’t shown the talent, cohesion, or coaching edge to keep pace with one of the league’s most complete rosters. Still, the NFL is rarely predictable. The Saints could stay competitive if they generate turnovers, hit on a few timely big plays, or exploit Buffalo’s vulnerable run defense. The reality is clear, though. They face an uphill battle against one of the league’s hottest teams.
*Watch NFL games LIVE with fuboTV (click for a free trial)*
Here we will look at and discuss some bold predictions for the game between the Saints and the Bills in Week 4 of the 2025 NFL season.
Dawson Knox leads Bills in receiving touchdowns
Josh Allen has a wealth of weapons at his disposal. However, tight end Dawson Knox remains one of his most trusted options in the red zone. Though he hasn’t scored yet this season, Knox has a history of stepping up when Buffalo needs him most. That's particularly true in tight coverage situations near the goal line.
Against a Saints secondary that has struggled to contain tight ends, Knox has the perfect opportunity to break out. With Keon Coleman and Khalil Shakir often drawing double teams, Knox could become Allen’s go-to target inside the 20-yard line. We have Knox finding the end zone and leading all Bills pass-catchers in touchdowns for Week 4.
James Cook gets three total touchdowns
James Cook has been one of the brightest stars of Buffalo’s unbeaten start. Through three games, he’s racked up 284 yards and four touchdowns on the ground. He has also averaged over five yards per carry. He’s also been a reliable receiving option. That makes him a dual-threat nightmare for opposing defenses.
The Saints, who have been vulnerable against the run, could be in for a long afternoon. Cook has a chance to tie a franchise record by scoring a rushing touchdown in his eighth straight regular season game. He just has the ability to score both on the ground and through the air. As such, a three-touchdown performance is well within reach.
Saints set a season high in rushing yards
If there’s one area where New Orleans can challenge Buffalo, it’s on the ground. The Bills’ defense has been dominant overall. However, their run defense has shown cracks, allowing more than six yards per rush. For a Saints offense desperate to keep Josh Allen on the sideline, establishing the run is essential.
Alvin Kamara should be leaned on heavily, with at least 20 carries to wear down Buffalo’s front. Kendre Miller could spell him for five to seven carries, and even quarterback Spencer Rattler could factor in with designed runs. If New Orleans can commit to pounding the rock, 125-plus rushing yards isn’t out of the question. Yes, it may not be enough to pull off an upset. That said, it could at least keep the game closer than expected.
Saints lose by two touchdowns
At the end of the day, the gap between these teams is too wide. The Saints’ defense is solid but lacks the depth to shut down Allen and his versatile offense for four quarters. On the other side, New Orleans’ offense has been among the league’s least productive. It is so hard to envision them scoring enough points to truly threaten Buffalo.
The Bills are favored by more than two touchdowns, and that feels justified. Buffalo should control the tempo from the start. Allen will dissect the secondary, and Cook will feast on the ground. Even if the Saints manage some success rushing the ball, they simply don’t have the firepower to match the Bills score for score. A 14-to-21-point margin wouldn’t be surprising by the final whistle.
Final thoughts
The Saints may find a few silver linings in Week 4. These may include a strong rushing output or defensive stops that slow down Buffalo’s rhythm. Still, those positives are unlikely to change the result. The Bills are rolling, and New Orleans doesn’t have the depth, scheme, or momentum to derail them.
Buffalo should cruise to 4-0, while the Saints fall to 0-4 and continue their search for answers. For New Orleans, this game is less about winning and more about showing they can compete.
