Bobcats coach Steve Clifford said Jefferson will be re-evaluated over the weekend.
"It's significant," Clifford said of having to play without Jefferson. "He's our best offensive player. I don't want to go crazy, but he's of the two or three best low-post scorers in the league."
Jefferson, who signed a three-year, $41 million contract this offseason, didn't participate in the morning shootaround and was seen walking around before the game with a noticeable limp.
Jefferson missed most of training camp after turning his ankle when he landed on Chris Bosh's foot during the team's second preseason game against Miami. Jefferson played in the regular-season opener at Houston on Wednesday night and had 13 points and eight rebounds in a loss.
Bismack Biyombo started for Jefferson, came up big for Charlotte scoring 11 points on 5-of-6 shooting and grabbing 10 rebounds.