Federer, who pulled out of the Paris Masters less than two weeks ago with a sore back, still showed some of the rust that plagued his opening loss to Gilles Simon. His first-serve percentage was higher than in his first match, but the shots still lacked some of their usual sting.
"It's been a tough week for me from the start,'' said Federer, adding his back was fine but that he had a stomach ailment after his match Monday night against Simon and felt "terrible'' when he woke up Tuesday. He spent the day in his room, trying to recover.
"It would have been impossible to play yesterday,'' he said, looking drained at his post-match news conference.
Stepanek was playing in the place of Andy Roddick, who withdrew from the tournament earlier Wednesday with a sprained ankle after losing his opening match Monday. Roddick said his injury did not appear to be serious, but that it left him unable to be competitive in Shanghai.
"Maybe I got lucky that Andy withdrew,'' Federer said. "And then Radek is not playing with his own rackets, so that made it a little bit more lucky again. I hope with a day of recovery, I'll make a miracle happen here and get through into the semis.''
The 26th-ranked Stepanek, from the Czech Republic, said he came directly to Shanghai from a vacation in Thailand to be an alternate. He had his tennis gear sent from home, but it hadn't cleared Chinese customs yet.
He had to borrow tennis rackets from Novak Djokovic and socks from Andy Murray, and needed to quickly buy contact lenses when he heard he was going to play.
Earlier, Murray reached the semifinals of the season-ending tournament by beating Simon 6-4, 6-2 in the other Red Group match. He quickly dismissed any suggestion that he might take it a little easy against Federer on Friday to save energy for the semifinals.
"I don't try and find a balance,'' Murray said. "I try and beat Federer. Ideally, I'd like to knock him out of the competition if I can. I'd rather not have to play him twice in one week. He's the best player ever.''
Stepanek started slow, winning only three points as he fell behind 2-0 in the first set, then took the next two games. But the Swiss star pulled ahead 4-1 in the tiebreaker and held on to take the set.
They were on serve in the second set until Stepanek faltered while serving at 4-3, with Federer breaking with a forehand volley winner off a floater.
But Federer, known as one of the best finishers in tennis, was broken back at love as he served for the match, netting a forehand after a long rally on break point.
Stepanek pumped his fist and hopped on one leg, but the Czech's celebration didn't last long. He missed a backhand volley to set up match point, then double-faulted. The loss eliminated him from contention for the semifinals.
Murray was at his best on the key points, breaking Simon twice in each set and fending off seven of the Frenchman's eight break opportunities.
"It was one of my best matches in recent months,'' said Murray, who recently won 14 straight matches.
Murray said he was nervous before the match, knowing that if he lost, he would have to beat Federer in his last round-robin match to qualify for the semifinals.
Both Murray and Simon were making their debuts at the tournament for the world's top players, but Murray looked like a veteran, winning the first four games. Simon won only four points in his first two service games.
The Frenchman did get one break back to pull within 4-3, but Murray fended off another break chance in his next and easily held to finish off the set.
Simon held to open the second set, but Murray took the next five games. On match point, the Briton ripped a deep forehand approach shot that Simon couldn't do anything with.
"I just missed all the opportunities I had today,'' Simon said. "He didn't miss anything.''
Simon was added to the field when Rafael Nadal withdrew last week with a knee injury that also forced the world's top-ranked player to pull out of next week's Davis Cup final between Spain and Argentina.
In the Gold Group, Nikolay Davydenko of Russia will face Juan Martin del Potro, with the winner assured of a semifinal spot. Novak Djokovic, who is 2-0, already has advanced and will meet Jo-Wilfried Tsonga of France, who has been eliminated after losing his first two matches.
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