Jefferson fell awkwardly to the court with 5:41 left in the third quarter when he landed on the foot of Heat center Chris Bosh as the two fought for rebounding position in the lane. Jefferson remained on the court for several seconds until a timeout was called so he could be treated by team trainers.
Teammates carried Jefferson to the locker room, where a Bobcats official confirmed the sprain after X-rays were negative. A dejected Jefferson had his right foot in a walking boot as he left the Sprint Center on crutches.
"It's sore as [expletive], real sore -- that's all I can tell you," Jefferson told ESPN.com as he left the arena. "It feels like I've got a heartbeat in it. All that matters is that it's negative. It ain't nothing I've never been through before, so I've just got to get treatment and make sure I'm ready for the season."
Bobcats coach Steve Clifford said significant swelling in Jefferson's ankle made it difficult to determine the extent of the injury or how much time the nine-year veteran might miss. But Jefferson will be out at least Saturday's game against the Milwaukee Bucks.
"I don't think they know how severe it is because of the swelling, but they're going to re-evaluate it [Saturday]," Clifford said after Friday's game. "Until then, I don't think we'll know [the extent]."
Jefferson had 11 points and seven rebounds in 23 minutes before he left the game. He had seven points and nine rebounds in 26 minutes during the Bobcats' preseason opener Tuesday against Atlanta. The Bobcats signed Jefferson to a three-year, $41 million contract this summer with hopes he would provide a spark to one of the worst teams in the league the past three seasons.
The 6-foot-10, 289-pound Jefferson has averaged 18.8 points and 10 rebounds per game the past seven seasons. During a nine-year career, Jefferson also played for Boston, Minnesota and Utah, and has career averages of 16.4 points, 9.0 rebounds and 1.5 assists a game.
The Bobcats were already dealing with injuries at center, with the team announcing Thursday that veteran Brendan Haywood will miss at least three months because of a stress fracture in his left foot. Those injuries along with a shortage of other big bodies could force rookie Cody Zeller, the fourth overall pick in June's draft, to shift from power forward to center until Jefferson returns.
Charlotte opens the regular season Oct. 30 at the Houston Rockets.