Varejao, who was injured in Wednesday's win over Washington, is averaging 10.9 points, 6.9 rebounds and is third in the NBA in field goal percentage, shooting 61 percent.
Varejao didn't practice Friday. He participated in Saturday morning's shootaround, but coach David Blatt said the 11-year veteran experienced discomfort and is being held out as a precautionary measure.
Tristan Thompson will start for the first time this season at center. He's averaging 8.7 points and 6.1 rebounds.
Both teams are short-handed in the frontcourt. Indiana center Roy Hibbert will miss his fourth straight game with a sprained right ankle.