The Celtics made the announcement minutes before tipoff, and assistant Damon Stoudamire took the floor as Boston's head coach in his absence.
Mazzulla addressed reporters earlier Tuesday in his pregame news conference, apparently intent at that point on coaching against the Rockets. Video from the news conference shows Mazzulla squinting and rubbing his right eye.
Whatever was bothering him apparently became too much to tolerate for a full game.
The Celtics beat the Rockets, 126-102. After the game, Stoudamire said he found out he was going to act as head coach around 10 minutes before tipoff. The extent of Mazzulla's injury remained unclear.
Mazzulla took over as head coach in September when the Celtics suspended Ime Udoka for the entire season, citing violations of the team's code of conduct. He has led the Celtics to the NBA's best record at 24-10. Boston entered Tuesday fresh off a Christmas Day victory over the Eastern Conference rival Milwaukee Bucks.
Despite the early success, the Celtics don't plan to remove his interim tag during the regular season, according to a Boston Globe report. It wasn't clear on Tuesday if Mazzulla would miss more time.