Doncic will undergo an MRI on Friday morning, sources told ESPN, and will not play later that night against the Rockets in Houston.
Two sources said the ankle injury, suffered when Doncic stepped on another player's foot, appears to be similar to the sprain he suffered earlier this season.
Doncic suffered the injury near the end of practice on Thursday and was getting treatment while coach Rick Carlisle addressed the media.
A source said Doncic stepped on a defender's foot while driving to the basket during a brief scrimmage.
Doncic, 20, who was voted to be the youngest All-Star starter since LeBron James in 2005, is averaging 28.8 points, 9.5 rebounds and 8.7 assists per game.