Novak Djokovic's US Open title defence just got a little tougher on Wednesday as a recent shoulder issue flared up and nearly knocked the Serbian out of a second-round match that tested his resolve.

Djokovic struggled with both his serve and backhand during a 6-4 7-6(3) 6-1 win over Argentine Juan Ignacio Londero and later said his left shoulder had been bothering him for weeks with the pain getting worse during the match.

"I've been experiencing some days of higher intensity of pain, some days less. It has been really fluctuating a lot, going up and down," said Djokovic.

"What happened today on the court, actually how I felt, was quite rough and unpredictable."

Djokovic, who had work done on the shoulder during his pre-match warm-up inside Arthur Ashe Stadium earlier in the day, was in clear distress when he took a medical timeout while leading 4-3 in the first set.

The Serbian ironman returned to court to close out the first set and then had more treatment before Londero, playing in only his second main draw match at Flushing Meadows, broke him twice for a 3-0 lead in the second.

So bothered was Djokovic by his backhand that in the third game of the second set, at 30-30 and with Londero well out of position, he failed to get even a soft backhand to the open court over the net.

But he roared back to take the next five games, a stretch during which he managed to fire off a number of backhand winners, en route to strolling through the tiebreak before getting more treatment on his shoulder.

"It was not easy to play with this kind of sensation, to be honest. I did not experience that too many times in my career," said Djokovic.

"The way it has started for me, especially midway through the first set, I didn't know if I would be able to finish the match."

While Djokovic was nowhere near his best, Londero, who is in the midst of a breakout season that saw him win his first title, will be happy to have played at such a high level in his first career meeting with the 16-times Grand Slam champion.

Up next for Djokovic, who has won four of the last five majors, will be either fellow Serbian Dusan Lajovic, the 27th seed, or American Denis Kudla, who were unable to play their match earlier because of inclement weather.

Djokovic said he would have the injury assessed on Thursday and hoped to be pain-free for his match on Friday.

"Good thing about Grand Slams is you have a day off in between the matches," said Djokovic.

"I'm hoping that with a proper medical help and treatments, I'll be able to get myself in a better state than I was today in a few days."