The Bills must brave New York without their star running back.

James Cook will be inactive for Monday’s tilt against the Jets due to a toe injury, NFL Network Insiders Tom Pelissero and Mike Garafolo reported.

Cook seemed to suffer the injury on a failed catch in the fourth quarter of a 23-20 Week 5 loss to the Texans, after which he sat out two practices this week. He managed limited participation Saturday and received a questionable designation, giving a glimmer of hope he could suit up, but he’ll instead miss the finale to Week 6.

Cook has carried his breakout from the end of last season into 2024 for Buffalo and is currently the team’s leader with 432 scrimmage yards and five scrimmage touchdowns.

Considering what’s at stake Monday and the slump Buffalo finds itself in, having scored 30 combined points across two straight losses after putting up 112 during its 3-0 start to the campaign, Cook’s absence looms large.

Whoever wins between the Bills and Jets on Monday Night Football assumes the AFC East lead a third of the way through the season, plus gains a potential edge for future tiebreakers.

New York’s defense is imposing in many aspects, but is somewhat lenient on the ground, where it ranks 14^th in yards allowed.

Instead of Cook, some combination of Ty Johnson and rookie Ray Davis will now be tasked with finding open space. Davis, who is tied with quarterback Josh Allen for second on the team in carries, has 75 yards and a score on 26 totes. He could be Buffalo’s grinder, while Johnson has shown a knack in the past for supplying receiving yards and has already caught a touchdown pass on one of his four receptions this season.

If the running game struggles sans Cook, Allen, who is himself struggling coming off a career-low 30% completion percentage versus Houston, must find a way to rebound against the Jets’ second-ranked passing defense.

He and the rest of the Bills will look to get back in the win column when Buffalo (3-2) and New York (2-3) kick off Monday at 8:15 p.m. ET.