The operation will repair a tear in the lateral meniscus of Jefferson's right knee. The team announced the injury after the start of Wednesday night's game against the Clippers.
Jefferson missed the matchup with Los Angeles for what Hornets coach Steve Clifford said was "some discomfort" in his right knee. Clifford said Jefferson underwent an MRI on Wednesday afternoon to determine the problem.
Jefferson had just returned to the Hornets' lineup after missing 11 games: six for a strained groin muscle and five for a suspension for violating the league's drug policy.
Jefferson was a reserve for Charlotte's previous two games, with underwhelming results. He had two points and four rebounds in 18 minutes against Memphis on Saturday, and three points and four rebounds in 15 minutes against the Lakers on Monday.
He is averaging 12.5 points and 6.1 rebounds in 19 games this season.