The Clippers arrived in Minnesota early Friday morning after a 122-91 loss to the Nuggets and decided to sit George and Leonard as a precaution after the quick turnaround.
Nicolas Batum also sat out because of a sprained left ankle.
The Clippers fell 128-115 to the Timberwolves for their fifth consecutive loss.
"It's tough when you're shorthanded the way we were tonight,'' Clippers coach Tyronn Lue said after Friday's loss. "I thought our guys competed and scrapped, and we were just overmatched at times."
Minnesota shot 56.8% from the field and scored 62 points in the paint. The Timberwolves led by as many as 25 despite 20 turnovers.
Los Angeles was allowing 109.8 points per game coming in, the fourth-lowest total in the league. Meanwhile, opponents were hitting just 45.8% of their shots against the Clippers.
"I just thought it was their ability to get into the paint [that] really hurt us," Lue said. "We were closing out all night on guys driving by us, allowed Rudy to get offensive rebounds and dunks because we couldn't control the ball and keep the ball in front of us."
The Associated Press contributed to this report.