"It felt like the first match I have ever played on the tour, very weird," he told reporters. "I just completely lost rhythm, everything, struggled a little bit with the health the last couple of weeks."
Djokovic took six months off after Wimbledon last year and returned in January's Australian Open where he lost in the fourth round. He had surgery in Switzerland shortly after that.
"I was grateful to be out on the court after surgery that quickly but at the same time just didn't feel good at all," he added. "Nerves were there. I made so many unforced errors."
Djokovic's performance in the final set against the world's 109th-ranked player on centre court raised some eyebrows, with four-times grand slam champion Jim Courier saying the Serb had "capitulated".
"The question marks surrounding his defeat today will only grow larger," Courier said in commentary on the Tennis Channel.
"We wondered post surgery what it was going to look like, how his elbow was going to react to the strain and stress, but it was his heart and head that didn't react the right way in this match. That is as head scratching as anything you'll see."
Holder Roger Federer avoided the same fate as Djokovic, though the Swiss top seed was pushed by left-handed Argentine Federico Delbonis in a match that was completed on Sunday after being halted by rain at 2-2 in the second set the previous day.
The top seed fended off a set point in the tiebreak to beat Delbonis 6-3 7-6(6).
"It's been a long time since I have been interrupted at night and have to come back the next day," said Federer.
"In the night-time, the ball is much more deader. The surface doesn't react so much."
Frenchman Gael Monfils survived a match point before beating big-serving American John Isner 6-7(5) 7-6(3) 7-5 in a contest that had only one break.
Isner, the 15th seed, frittered away seven break points, while Monfils converted one of his three opportunities, which proved enough.
Yuki Bhambri of India pulled off a surprise when he toppled ninth-seeded Frenchman Lucas Pouille 6-4 6-4.
Israeli Dudi Sela beat British 21st seed Edmund 6-4 6-4, while Luxemburg's 24th seed Giles Muller was upset by Frenchman Pierre-Hugues Herbert 6-3 7-5.
In late action, Croat second seed Marin Cilic beat Hungarian Marton Fucsovics 7-5 6-3, while Canadian Milos Raonic defeated 17-year-old compatriot Felix Auger-Aliassime 6-4 6-4.
"I was attacking when I had my chances and controlling most of the times the points," said Cilic. "I didn't serve too good today but overall I'm pleased."
The tournament also lost Japan's Kei Nishikori, who withdrew through illness.
(Reporting by Andrew Both in Cary, North Carolina; Additional reporting by Gene Cherry; Editing by Peter Rutherford)
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