Jefferson's suspension will begin with the next regular season game for which he is eligible and physically able to play, the NBA said in a statement.
The league disclosed no further details about his violation, though according to the terms of the agreement between the NBA and its Players' Association, players are suspended for five games following a third positive marijuana test.
"We are disappointed in Al's decisions that led to this suspension," the Charlotte Hornets said in response to Jefferson's five-game ban.
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"As an organization, we do not condone this behavior. We have addressed this with Al. He is regretful and understands that we expect him to learn from this mistake."
Taken 15th overall by the Boston Celtics in the 2004 NBA draft, Jefferson is averaging 13.7 points and 6.4 rebounds per game for the Hornets this season, having started in all 17 games he has played.
However, he has not competed for the team since Nov. 29 when he exited during the first quarter of a game against the Milwaukee Bucks because of a left calf strain.
Jefferson, 30, said in a statement: "I want to apologize to the Hornets organization, our owner, my teammates and my coaches for the poor decision that I made.
"I know I have let people down, especially the Hornets fans that have been so supportive of me since I arrived in Charlotte two years ago. From the bottom of my heart, I am truly sorry, and I am committed to making smarter decisions in the future."
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