Wilkerson injured a toe in Monday night's 38-3 loss to the Buffalo Bills and was in a walking boot Wednesday as the Jets (2-9) began preparations for the Dolphins.
It's not a fracture, according to coach Rex Ryan, who described the injury as similar to turf toe.
"It doesn't look good for Big Mo," Ryan said. "If you're in a boot, that doesn't look good for this week. But, hopefully, we'll get him back as soon as we can."
The early indications are that Wilkerson could miss at least a week or two.
Wilkerson, a first-round pick in 2011, has never missed a game. He's arguably the Jets' top defensive player, a second-team All-Pro in 2013. He leads the team with 4.5 sacks.
Ryan said the worst case of turf toe belonged to former Baltimore Ravens star tackle Jonathan Ogden, a Hall of Famer who was forced to retire after the 2007 season.
"I'm not saying Mo has to retire," Ryan said, laughing. "Oh, my goodness, we don't want that. That's not happening."
Quinton Coples, a hybrid linebacker/lineman, is expected to replace Wilkerson at defensive end.
There's a chance the Jets also could be without defensive tackle Sheldon Richardson (back), although Ryan expressed optimism that last year's NFL Defensive Rookie of the Year will be able to go. Richardson has 3.5 sacks and leads the team with 29 quarterback hits.
Richardson's back stiffened against the Bills. He didn't finish the game and didn't practice Wednesday.
Rookie tight end Jace Amaro, placed in the NFL's concussion protocol with a head injury, is unlikely to play. The Jets already are planning for the possibility of signing tight end Chris Pantale from the practice squad.