Novak Djokovic has hailed Alexei Popyrin as a legitimate US Open title contender after the audacious Australian rocked the Serbian superstar's grand slam dreams in New York.

Djokovic rued "some of the worst tennis I have ever played" after coughing up 14 double-faults in his 6-4, 6-4, 2-6, 6-4 third-round loss to Popyrin on Saturday (AEST).

"Honestly, [my] serving [was] by far the worst ever," he said.

But the 24-time grand slam champion cast aside the disappointment of being unable to continue his quest for an unprecedented 25th major to label Popyrin as a potential US Open winner.

"Look, he's just beaten me, the defending champion here," Djokovic said when pressed about Popyrin's prospects.

"So he deserves credit for that and respect. If he serves well, plays well, he can beat anybody.

"[Carlos] Alcaraz is out. I'm out, you know, some big upsets. The draw is opening up.

"Obviously [Jannik] Sinner is the main favourite but then [Frances] Tiafoe is there as well as American favourite [Taylor] Fritz.

"[Alexander] Zverev, you have great guys playing well, and [Andrey] Rublev, [Grigor] Dimitrov in this part of the draw.

"Anybody can take it. It's going to be interesting to see who takes the title in the end."

For all his brave front, Djokovic could not disguise his dejection at blowing his latest opportunity to surpass Margaret Court's joint-record of 24 grand slam singles crowns.

Despite joining Rafael Nadal, Andre Agassi, Steffi Graf and Serena Williams as only the fifth tennis player to complete the fabled Golden Slam with an elusive victory at the Paris Olympics, Djokovic has now, for the first time since 2017, gone a year without winning a major.

At 37, the clock is ticking on his chances of surpassing Court and becoming the first and only player with 25 grand slam singles crowns under their belt.

"Obviously fresh off the court, you have a bitter taste in your mouth and you don't like losing, even though I had so many more wins than losses in this tournament and really any other," he said.

"So I have to draw the line. Sitting from a larger perspective, of course I have to be content.

"It's hard to see the big perspective right now. You're just angry and upset that you lost and the way you played and that's it.

"But tomorrow is a new day and I will obviously think about what to do next."

Djokovic opted against playing any lead-up events after claiming Paris gold, sitting out the Montreal and Cincinnati Masters events he has won numerous times before previous US Opens.

"You could argue that it's because of the Olympics, but I don't know," he said.

"I don't want to analyse that right now. I was just looking to really improve my game here on a daily basis, but it just didn't happen.

"I tried so many things and sometimes that's an issue, that you move away from the basics that work.

"Then you just lose the basics. You lose the foundation. You lose the movement, the timing, the rhythm, the tempo, everything, whether it's a serve or any other shot.

"It was just really a big struggle mentally for me to play these three matches here because I wasn't playing even close to my best."

AAP