Watkins, the fourth overall pick in May's draft, bruised his ribs in last Saturday's preseason loss to the Pittsburgh Steelers. He was limited in four practices this week, although the rookie downplayed his injury and said he felt ready to play in a game.
"I'm fine, I could go out there and practice if I need to," Watkins said after Tuesday's practice. "But the thing is doing it without pain, but I could play a full game right now. It's just being safe."
But after Saturday's game, Bills coach Doug Marrone had a message for the rookie: "I told Sammy that you can't talk about injuries," Marrone said. "That's what gets you in a bind and it doesn't make us look good when you start saying those things. The doctor, at the end of the day, said he couldn't play."
Without Watkins, the Bills used Mike Williams, Robert Woods and Chris Hogan as their first-team receivers with quarterback EJ Manuel. Watkins may also sit out Thursday's preseason finale against the Lions.
Williams accounted for the team's only receiving touchdown in the loss.