Coach Erik Spoelstra said that Wade, who played 21 minutes and scored two points in the Heat's win over Milwaukee on Tuesday, would test his shoulder before the game. Miami declared him out about a half-hour before tipoff.
Halfway through the second quarter, starting center Hassan Whiteside abruptly fell to the floor with a strained left oblique and did not return to the game.
Another starter, Luol Deng, left the floor with a towel covering his face after being poked in his right eye with 2:25 to play. He finished with 16 points.
"When it's another guy going down it's just tough," said Chris Bosh, who led the Heat with 18 points. "Two weeks ago we were going into a West Coast road trip really trying to prove ourselves with a whole roster, and now we've got five or six or seven guys out, and it's just a tough pill to swallow."
Wade sat out his second game in the past four.
"I just think it's very inflamed right now," Wade said of his shoulder. "It needs to calm down, so it's going to be a day-to-day process. It's very unfortunate because we're down so many bodies, but you know you got to do what's best."
Information from The Associated Press was used in this report.