Sinner, who was targeting a maiden French Open title and career Grand Slam in the absence of his injured rival Carlos Alcaraz, was hampered by illness for a 3-6 2-6 7-5 6-1 6-1 second-round defeat by Juan Manuel Cerundolo.
After titles in Monte Carlo, Madrid and Rome, and a comfortable victory in his Paris opener, Sinner fell flat on Court Philippe Chatrier.
"In general, many things came together... I played a lot, and I didn't have a lot of time to recover," Sinner said in a packed press conference room.
"I came here, first match, really good, really solid... even though I finished late, but not crazy late.
"This morning I didn't sleep well. When I woke up, I was struggling a bit, but this can happen. Usually, in Grand Slams, you have a couple of days where you don't feel perfect.
"That was today."
While heat and humidity have often tripped up Sinner during big events, the world number one, who hails from northern Italy's South Tyrol, said he was at ease in Paris despite the mercury going past 30 degrees Celsius.
"Shanghai (in October) was very tough. The humidity was high," Sinner said about his retirement in the Chinese city.
"Australia was very warm (this year), I remember. It's different when you play on hardcourts, because the heat also comes from underneath," Sinner explained.
"Here, it was warm, but it was okay. It wasn't like I was dying because of the heat. Today, it was a completely different scenario, but this can happen.
"It's tough to accept, of course, because of the position I've been in and everything considered, but now I have a lot of time to recover."
Sinner said he would consider skipping grasscourt tune-up tournaments before his title defence begins at Wimbledon, where the main draw gets underway on June 29.
"I won't play any tournament on grass before (Wimbledon), most likely," he added.
"I really need some time off to recover completely, also mentally, and then be ready to go again."
