The Heat downgraded James from a game-time decision to doubtful 90 minutes before tipoff and James Jones was started in his place. The Nuggets won 130-102.
Heat coach Erik Spoelstra said the hope is a couple of days off would allow James to return to the lineup Saturday in Chicago when the team closes its five-game road trip against the Bulls.
James suffered the injury Wednesday night in Los Angeles when he rolled his ankle on a drive to the basket in the fourth quarter.
James finished the game, a 111-105 loss to the Clippers, but clearly favored the ankle.
When James arrived at the Pepsi Center he was wearing a flip-flop on his left foot, likely because of swelling in the ankle. Earlier he posted a message on his Twitter account indicating he'd gotten some bad news, writing: "The longer we dwell on our misfortunes, the greater is their power to harm us."
James had suffered a series of ankle sprains during his career and usually it has only caused him to miss a game or two. James said Wednesday night, when he had X-rays that showed no break, that doctors didn't believe it was a serious sprain.
It will be James' first missed game of the season.
Brian Windhorst covers the Miami Heat for ESPN.com.