Murray, playing his first match since his triumph at the London Games on Sunday, called out a trainer late in a 6-1 6-3 win over Italian Flavio Cipolla, which he later attributed to a change of playing surfaces from grass to a hard court.
"I feel on the grass courts the muscles get tired but the joints not so much, but on the hard courts the knees, ankles and hips take quite a fair pounding," Murray, whose match was his first on a hard court since early March, said.
"And because I haven't had enough days to adjust to the surface that's probably why there were a few aches and pains."
The Briton, who appeared to hurt himself while chasing down a forehand, occasionally rubbed his left knee and had about five minutes of massage on his left quadriceps while leading the final set 3-2.
Still, the second seed, who is scheduled to face big-serving Canadian Milos Raonic in the third round, managed to chase down drop shots and held his serve throughout the 82-minute match.
Defending champion Novak Djokovic cruised to a 6-2 6-3 win over Australian Bernard Tomic in 71 minutes, setting up a third-round match with American Sam Querrey, who upset 13th seed Kei Nishikori of Japan 6-2 6-3.
Third seed Frenchman Jo-Wilfried Tsonga was the highest seeded player eliminated on Wednesday, falling 6-4 7-6 to compatriot Jeremy Chardy.
Del Potro, whose Olympic semi-final loss to Roger Federer five days ago was the longest men's three-set match played in the professional era, admitted fatigue got the better of him during a 6-4 7-6 defeat to Czech Radek Stepanek.
"It's not easy to play after a big effort in the Olympics," the sixth seeded Argentine said. "Now I need time to recover my body if I want to stay healthy."
Del Potro, who was playing his first match since beating Djokovic for the bronze medal at the Olympics on Sunday, also said he had no doubt he would be ready for the August 27-September 9 US Open, where he won his sole Grand Slam in 2009.
In other action, fourth seed Tomas Berdych rallied for a 6-7 6-4 6-4 win over Julien Benneteau in a match that lasted just over three hours, while ninth seed Gilles Simon fell 6-2 6-2 to Germany's Tommy Haas.
Fifth seed Janko Tipsarevic of Serbia was a 7-6 6-4 winner over Russia's Mikhail Youzhny, Croatian 10th seed Marin Cilic breezed by Greece's Marcos Baghdatis 7-5 6-3 and German 15th seed Florian Mayer fell 6-3 6-4 to Spain's Marcel Granollers.
- Novak Djokovic