Del Potro says he suffered a similar problem in Miami earlier this year
Concerns over the length of the season increased when Juan Martin del Potro became the latest high-profile player to withdraw from the Shanghai Masters.
The US Open champion was forced to retire from his second-round match against Jurgen Melzer at 5-7 1-2 because of a wrist problem.
Tommy Haas also retired injured from his match to join Andy Roddick in quitting the event.
Meanwhile, Rafael Nadal beat James Blake 6-2 6-7 (4-7) 6-4 to progress.
The world number two has also been outspoken about the demands of the tour, saying: "It's impossible to play 1 January and finish 5 December."
However, the Spaniard, who did not defend his Wimbledon title this year because of a knee injury, showed few signs of fatigue as he battled past American Blake in a little over two hours.
Injuries to Del Potro, Roddick and Haas, though, are sure to increase pressure on the ATP to look at the year's schedule.
Both world number one Roger Federer (fatigue) and Britain's world number three Andy Murray (wrist injury) had already skipped the tournament.
Roddick, who has described the tour schedule as "ridiculous" and has yet to qualify for next month's World Tour finals in London, withdrew from his match against Stanislas Wawrinka with a knee injury on Tuesday.
Haas was forced to retire at the end of the first set of his tie against German compatriot Rainer Schuettler at 4-6 down because of a right shoulder injury.
And Del Potro, who said that he suffered from similar wrist tendinitis earlier in the year, pulled up in his match against Melzer to ensure only two of the top six players are left in the draw.
"It's a big tournament here in Shanghai, very important for me," said the Argentine. "But if I want to have a good finish this season, I have to recover, go home to be in good shape for the last tournaments."
Czech Tomas Berdych, meanwhile, ended the Asian portion of Marat Safin's career, with the Russian set to retire in a month, as he came through 3-6 6-4 6-4.
But the Russian was not happy, accusing Berdych of feigning injury when behind in the second set and adding: "If you're losing, just be a man and lose as a man. Don't pretend that you are injured and then you start running around and start to hit winners.
"I mean, what kind of sportsman are you? What kind of man are you?"
In the last match of the day, Serbian number two seed Novak Djokovic easily saw off Italy's Fabio Fognini 6-3 6-1.
Before that, Frenchman Gilles Simon, seeded eight, beat Serbia's Viktor Troicki 6-3 6-4.
And elsewhere, former Shanghai champion Lleyton Hewitt lost to Gael Monfils as the French 11th seed knocked out the Australian 4-6 6-4 6-2.
But 28-year-old Hewitt, who extended his career through hip surgery last year, refused to fully join the controversy over the 11-month ATP season.
"We're all human and we're going to get injured at times - no one is Superman out there," he said. "You can't keep putting your body through it all the time at these levels.
"But players know their bodies better than anyone, and especially the top guys. And the tour needs the top guys. The players shouldn't be obliged to play all the tournaments every week - they know what it takes to be the best in the world."
Tommy Robredo, the 14th seed, beat Florian Mayer 4-6 7-6 (7-1) 6-4, while his fellow Spaniard Feliciano Lopez defeated compatriot David Ferrer, the 16th seed, 4-6 7-5 6-1.
Sweden's French Open finalist Robin Soderling reached the third round over Nicolas Almagro of Spain 6-4 7-5.