The world No 1 needed four tough sets to beat Jerzy Janowicz in the first round last Monday.
But he skipped the second round when Jiri Vesely handed him a walkover with an arm injury before Mikhail Youzhny lasted just six games and 32 minutes before calling it quits with a hamstring injury in Friday’s third round.
World number 84 Edmund, by contrast, is battle-hardened having defeated top 20 seeds Richard Gasquet and John Isner to make the last 16 for the first time.
“Considering the stage of the season, the amount of matches I’ve played, what I’ve been through with my body, I think it’s actually good to have some days off and then shorter matches,” said Djokovic, chasing a third major of 2016.
“But, again, I’m not too concerned about my game itself. I’ve worked hard last couple days. Health-wise I feel much better than I did at the beginning of the tournament. I’m confident that everything is going in the right direction.”
Edmund, 21, was one of three British men to make the third round – the first time that there have been so many at that stage in New York since 1968.
Edmund said he hopes to take positives from his only previous meeting with the Serb, a 6-3, 6-3 loss in Miami this year.
“He’s obviously a great player. He’s tough to break down. Makes a lot of balls. Very quick around the court. He has lots of good abilities. He’s world No 1. He’s good in all areas,” said the Johannesburg-born Briton.
Fellow two-time champion Rafael Nadal also chases a quarterfinal spot on Arthur Ashe Stadium on Sunday. The fourth seed tackles French 24th seed Lucas Pouille.
Nadal beat Pouille comfortably in their only other previous meeting in Monte Carlo last year where he gave up just three games.
Nadal has been impressive in New York and has shown few signs of the wrist problems which sidelined him from midway through the French Open until the Olympics.
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