Rose has missed the past seven games due to a sprained left ankle, the latest ailment he has suffered during his career. The repeated injuries are weighing on Rose with a team source telling ESPN, "He's tired of being hurt and it's taking a toll on him mentally."
Rose was the 2011 NBA MVP as a member of the Chicago Bulls before multiple knee injuries derailed his career.
He is in his first season with Cleveland and was last seen around the team on Monday.
The Cavaliers said that Rose's current absence is excused.
Rose, 29, originally suffered the ankle injury on Oct. 20. He returned to play in five games but suffered a setback on Nov. 7 and hasn't played since.
He was placed in a walking boot last week when the ankle wasn't deemed to be healing sufficiently.
Rose, a three-time All-Star, is averaging 14.3 points, 2.6 rebounds, 1.7 assists and 2.7 turnovers in seven games this season.
Last season, Rose disappeared from the New York Knicks without notification and missed a game, later saying it was related to a family matter.