Roger Federer revealed he struggled in the hot conditions for one of the first times in his career during his shock US Open loss to John Millman.

The second seed was uncharacteristically poor on his way to bowing out 3-6 7-5 7-6 (9-7) 7-6 (7-3) against Millman in the fourth round at Arthur Ashe Stadium.

Federer appeared lethargic for much of the encounter, leading to suggestions he was not fully fit or perhaps unwell.

But the 20-time grand slam champion said the hot and humid conditions in New York simply got the better of him.

"I just thought it was very hot. It was just one of those nights where I guess I felt I couldn't get air. There was no circulation at all," Federer told a news conference.

"I don't know, for some reason I just struggled in the conditions. It's one of the first times it's happened to me.

"Yeah, it's uncomfortable. Clearly just keep on sweating more and more and more and more as the match goes on. You lose energy as it goes by.

"But John was able to deal with it better. He maybe comes from one of the most humid places on earth, Brisbane. I knew I was in for a tough one. Maybe when you feel like that, as well, you start missing chances, and I had those. That was disappointing.

"But, look, at some point also I was just happy that the match was over, I guess."

Federer endured huge struggles with his usually reliable serve, finishing with a first-serve percentage of 49.

The Swiss star also squandered two set points in the second, a crucial momentum change as Millman levelled the match, and Federer lamented that missed opportunity.

"I do believe since the roof is on that there is no air circulation in the stadium. I think just that makes it a totally different US Open," he said.

"Plus conditions maybe were playing slower this year on top of it. You have soaking wet pants, soaking wet everything. The balls are in there, too. You try to play. Everything gets slower as you try to hit winners.

"I thought the match was tough. I wish I could have led two sets to love and then maybe the match would be different, and I would find a way, because I did have my chances all the way till the end. It was just tough. I thought John played a great match in difficult conditions."