The injury management strategy on the second night of a back-to-back means James will miss his 18th game of the season and won't be eligible for season awards. James last failed to make an All-NBA squad in 2003-04, his rookie season with the Cleveland Cavaliers.
He'll be joined on the sidelines by teammates Luka Doncic, Austin Reaves, and Marcus Smart.
Doncic will miss his third straight game with a hamstring strain, Reaves will sit out the second night of a back-to-back as the team manages the calf injury that sidelined him for 19 games, and Smart is out with a sore right ankle.
Injuries have been a key factor as the Lakers struggled for consistency this season. But after Monday's loss to the NBA champion Oklahoma City Thunder, James was blunt in his assessment of Los Angeles' shortcomings, and he didn't use injuries as an excuse.
"You want me to compare us to them," he said. "That's a championship team right there. We're not.
"We can't sustain energy and effort for 48 minutes, and they can. That's why they won a championship."
James scored 14 of his 22 points in the second half on Monday, but after 35-plus minutes on court, he admitted he was feeling the strain.
"I'm tired," he told reporters after the Lakers saw a three-game winning streak end.