The Bulls announced late Tuesday night that the oft-injured point guard will undergo surgery to repair a medial meniscus tear in his right knee.
Rose will have a third knee procedure in three years. The 2011 NBA MVP previously missed the entire 2012-13 season recovering from a torn ACL in his left knee, an injury that occurred in Game 1 of the Bulls' Eastern Conference quarterfinals series against Philadelphia.
He made a long-awaited return to the court last season, but had it cut short after just 10 games after tearing the meniscus in his right knee.
Rose had been generally healthy this season, having appeared in 46 of Chicago's 57 games. The three-time All-Star told the team earlier Tuesday he was experiencing pain in the surgically repaired knee, and an MRI taken afterward revealed the tear.
There is no timetable for a return.
The Bulls own a half-game lead over LeBron James and the Cleveland Cavaliers in the Central Division. Chicago has won two straight, six of its last seven and four straight as the host. Wednesday's tilt is the third of a seven-game homestand which awaits visits from the Minnesota Timberwolves, LA Clippers, Washington Wizards and Oklahoma City Thunder.
The Bulls squashed the Milwaukee Bucks, 87-71, on Monday.
Tony Snell had 20 off the bench, his third 20-point game over his last five after just one such previous game in his career. Nikola Mirotic also played well as a reserve, tallying 16 points and 14 rebounds. Both players got extended minutes with sixth man Taj Gibson sitting with an illness.
Chicago won the rebounding edge, 62-41.
"We hit the glass pretty well," said Noah.
The Hornets are a mess, the losers of five straight. They've slipped a game behind the Brooklyn Nets for the eighth playoff seed in the Eastern Conference and still have trips to Boston and Orlando on this trek.
On Sunday, Charlotte began the excursion with a 92-81 loss to the Dallas Mavericks.
"(Williams) is a pro player, he's a good offensive player," said Hornets coach Steve Clifford. "He's doing a good job."
Michael Kidd-Gilchrist also had 15, while Lance Stephenson chipped in 11 off the bench.
The Hornets led 4-2 on a Kidd-Gilchrist dunk 2:06 into the game. Jefferson hit a 3-pointer at the other end and Dirk Nowitzki scored five straight, and the Mavs led the rest of the way.
The Bulls have taken six of the last seven meetings and three straight at home.