LeBron James is also battling a cold but is expected to play.
Wade sprained his right ankle in the Heat's loss Friday night in Denver and missed practice the last two days. He has also been battling a sore left foot, which caused him to miss three games earlier this season, and a calf strain that he suffered last week.
Heat coach Erik Spoelstra, who announced that Wade would be unavailable, has not set a timeline for when the team thinks Wade could be back. Miami hosts the Los Angeles Lakers on Thursday and the Philadelphia 76ers on Saturday.
James got sick following the Heat's five-game road trip that ended in Denver.
"I've felt better," James said. "It was a long road trip and it got the best of me."
The Heat are 3-0 this season without Wade, as James and Chris Bosh have stepped up their offensive games when Wade has been out. James has averaged 35 points in two games without Wade and Bosh has averaged nearly 26 points in three games without him.
James Jones will likely start in Wade's place but Spoelstra hinted Tuesday morning that Mike Miller will be activated for the first time this season. Miller has been out since the start of training camp following surgery to repair a sports hernia.
Brian Windhorst is an NBA writer for ESPN.com.