The Lakers said the move is being made to ensure that the groin injury suffered by 34-year-old James in a Christmas Day game can fully heal.
"After consulting with our team doctors and medical staff, we have decided to hold LeBron out of games for the remainder of the season," Lakers executive Magic Johnson said in a statement.
"This decision will allow his groin to fully heal, and is best for the future success of both LeBron and the Lakers."
In his first season with the Lakers, James averaged 27.4 points, 8.5 rebounds and 8.3 assists but was limited to just 55 games because of the injury.
The Lakers, 34-42, were officially eliminated from playoff contention last week, marking the first time since 2005 that James has failed to make the playoffs.
He had reached the NBA Finals eight straight years with the Miami Heat and Cleveland Cavaliers, winning three titles in that span.