The duo are due to face-off for the 30th time in their careers, but the first since last years Australian Open final.
Serena eased through her previous match against Carina Witthoeft, winning 6-2 6-2 against the German, while Venus defeated Italys Camila Giorgi 6-4 7-5 in the midday heat at Flushing Meadows.
I dont know how they do it honestly, said Djokovic after he booked his own place in the third round with a four-set win over Tennys Sandgren.
I mean, I have utmost respect for both of them. I have two younger brothers. I was kind of imagining what it would be like if I had to play one of them. I mean, I dont know really.
Thankfully I wont experience that because I dont know if I would be able to kind of be that fierce competitor against my brother.
But they manage to do it. I mean, they play, as you say, 30 times. Thats something that its really impressive.
As I said, respect. Respect for both what they have done in their careers and to see them play at their age still, keep on going. Its inspirational really for all of us.