Cavaliers coach Tyronn Lue said at the team's morning shootaround Saturday that Irving would sit out the game. The last time Irving took a game off was on Dec. 29 in Denver.
Irving has played in 46 games, all starts, since returning from a broken kneecap sustained during last year's NBA Finals.
Irving is coming off a 6-of-22 shooting performance in a 104-95 loss to the Brooklyn Nets on Thursday night. He is averaging 19.4 points and 4.5 assists this season.
Matthew Dellavedova will make his 12th start on the season.
Lue also said guard Mo Williams could return from a left knee injury for the first time in over a month.
Lue said this week that he will prioritize resting his players before the playoffs with the Cavs having already clinched the Central Division title.