Coach Rick Carlisle told reporters after Wednesday's shootaround that Nowitzki would not play against the Minnesota Timberwolves thanks to an ailment the team is officially listing as right knee effusion.
Carlisle said the team isn't certain about the cause of the injury or whether the Nowitzki, 37, would be sidelined multiple games.
"He's out [Wednesday]. That's all I can tell you," Carlisle said. "We'll see where we are tomorrow and the next day."
Nowitzki, who leads the Mavs with 17.8 points per game in his 18th NBA season, has had problems with his right knee in the past. He missed the first 27 games of the 2012-13 season after undergoing arthroscopic surgery on the knee.
Reserve guard Raymond Felton is also out against the Timberwolves because of an eye injury.