Heat coach Erik Spoelstra said James will benefit from the night off to deal with some minor injuries as Miami prepares for the start of the playoffs this weekend.
James has been dealing with periodic back soreness throughout the season and recently aggravated an ankle sprain. It will be just the third game of the season James has missed, with the Heat holding a 2-1 record in those absences this season.
Like James, Bosh spoke after Saturday's loss in Atlanta about a need for some time off before the playoffs. Bosh is having his least productive month of the season in April, averaging just 12.1 points and struggling with his perimeter shot.
Spoelstra said James and Bosh will be reevaluated again before Wednesday's home game against Philadelphia before determining their status for the regular season finale.
Though long guaranteed a spot in the playoffs, the Heat still have a chance to earn the East's top overall seed as they sit a half-game back of first place Indiana.