World number six Andy Roddick pulled out of the $4.45 million Masters Cup on Wednesday because of a right ankle injury.
The 26-year-old American lost his opening match in the season-ending championship for the world's top eight players to Andy Murray on Monday and was due to play top seed Roger Federer in his second group encounter later on Wednesday.
"It was during a warm-up drill in practice yesterday," he told reporters.
"I can't really stop or start quickly. It's definitely a tough prospect trying to beat Roger and not being able to move much."
First alternate Radek Stepanek, the Czech world number 27, will step in to take on Federer after Briton Murray has taken on Frenchman Gilles Simon in the opening Red Group match of the night.