The starting quarterback sustained a knee injury, while Johnson took a knock to his back.
Head coach Doug Marrone told reporters: "EJ has a sprained knee so we'll look at that and then obviously Stevie his back, you lose those two guys it's difficult.
"I saw [Manuel] working out on the sideline [and] thought we probably could get him back and then [the medical team] shut him down and said, 'Hey, listen. We're not going to put him back in there'. We're going to take a good look at it when we get back to Buffalo."
The Bills went on to lose the game 37-24.