Coach Frank Vogel made the announcement that his star player was out about 90 minutes before tipoff. He said James woke up with some soreness in his left knee. The team had listed James as questionable earlier Thursday before he was ultimately ruled out.
Vogel says James is day-to-day, meaning his availability for Friday's matchup in Charlotte is in question.
James had played in 25 straight games for L.A. after missing 12 of the first 23 this season because of right ankle soreness, a suspension and a false positive result on a COVID-19 test. The Lakers are now 5-8 without him in the lineup compared to 19-17 with him.
Tuesday's win in Brooklyn was the 18th straight game in which James scored 25 points or more.
"I'm in one of the best zones offensively I've been in, in my career," the 19-year veteran said recently.
James is one game from passing the late Kobe Bryant on the career games played list. Two years ago this week, James passed Bryant in career points in Philadelphia just before Bryant, his daughter Gianna and seven others died in a helicopter crash.
The Lakers welcomed Anthony Davis back from a 17-game absence Tuesday and signed forward Stanley Johnson to a contract for the remainder of the season, including an option for next season, on Thursday.