Kyrgios, playing his first tournament since he retired in the first round of Wimbledon due to a chronic hip injury, said mental problems and physical struggles had hurt his preparations.
"Just struggling, mentally, physically," Kyrgios told reporters later.
He had called out the medical trainer for treatment on his shoulder before retiring and looked in obvious discomfort.
Kyrgios was playing in the second round after receiving an opening round bye and was seeded to play Germany's Alexander Zverev in a keenly anticipated third-round match.
Earlier, 20-year-old Zverev needed three sets to overcome serve-and-volleyer Jordan Thompson 4-6 6-3 7-6(5) to advance as the Australian dropped the last three points of the decisive tiebreaker including his first double fault of the match.
"I'm just happy to get through that one," said the fifth-seeded German, a three-time winner this year.
Also failing to advance was defending champion Gael Monfils, as the sixth-seeded Frenchman was upset by qualifier Yuki Bhambri of India 6-3 4-6 7-5.
Bhambri, 25, will move on to face Argentina's Guido Pella in the round of 16.
Canada's big-serving Milos Raonic triumphed 7-6(2) 7-6(8) in a hard-fought match against France's Nicolas Mahut and set a tournament record with a 151 miles per hour rocket among his 26 aces.
Raonic, the 2014 winner, is looking for his first 2017 title.
"It's a big chance to turn things around," he said.
On the women's side, French second seed Kristina Mladenovic needed nearly two and a half hours in her first match, winning five of the last six games to beat Germany's Tatjana Maria 7-5 3-6 6-3.
Canada's unseeded Eugenie Bouchard scored her first win since Roland Garros with a 7-6(6) 6-0 win over eighth-seeded American Christina McHale.
(Reporting by Larry Fine in Safety Harbor, Florida; Editing by Sudipto Ganguly)
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