His right toe is still sore and the team doctor said a night of rest would help, Cleveland coach Mike Brown said after shootaround Friday.
"If it was a playoff game he could play," Brown said. "The doctor suggested it would be good to give him the additional rest. It's just sore."
Brown said he did not expect James to miss Sunday's home game against the Phoenix Suns (ABC, 1 p.m. ET).
James, who leads the voting for next month's All-Star Game, originally injured his toe on a West Coast swing earlier this month. He aggravated it in a double-overtime home loss to the Sixers on Wednesday, skipping a team workout Thursday and recording an appearance on the "Late Show with David Letterman" in New York.
Cleveland started out the New Year with four straight wins but has lost five of six games.
In Wednesday's loss, James scored a season-high 39 points, including 13 in the second overtime.
The Sixers are coming off consecutive wins for the first time since late December of last year.