Wade has been dealing with at least three lower-leg injuries in recent weeks, and sprained the ankle late in Miami's loss on Friday at Denver. He also has been battling a sore left foot and a strained calf muscle.
Tuesday's game will be the fourth Wade has missed this season. Miami won all three of the previous contests without the 2006 NBA Finals MVP, who turned 30 on Tuesday.
Wade did not practice Sunday or Monday, though went through some treatment and conditioning both days. Heat coach Erik Spoelstra says there is no timetable for Wade's return.
Miami next plays Thursday at home against the Lakers.