The 24-time Grand Slam champion was making his comeback from a shoulder injury in the last big tournament before the French Open.
Djokovic was playing for the first time since losing in the last 16 at Indian Wells in March, having pulled out of tournaments in Miami, Monte Carlo and Madrid.
The 38-year-old had not been knocked out this early in a tournament since the Madrid Open last year, and looked a long way from the player who has won six Rome titles.
“I don’t think I played so bad to be honest,” Djoovic told reporters.
“It was OK, it was a good battle in the end but obviously I see what I’m missing. I’m late half a step. I’m not definitely where I want to be for the highest level to compete.”
Djoovic added that he hopes he can be in good condition for Roland Garros which starts later this month, saying “let’s see what happens”.
Playing with a shoulder brace, Djokovic had breezed through the first set helped by Prizmic’s 13 unforced errors.
But the world number four’s hitting started to look increasingly tentative as Prizmic rattled off four straight games at the start of the second set with his powerful ground strokes finding their mark.
Prizmic came to the Italian capital with a career-high ranking of 79 after reaching the third round in Madrid—beating world number six Ben Shelton in the process — and had also dispatched Marton Fucsovics to set up his clash with Djokovic.
The 20-year-old reached the third round of a second consecutive Masters 1000 event with the biggest scalp of his career to date.
Djokovic is Prizmic’s idol, and a landmark win gives the young talent a match with either Ugo Humbert or Vit Kopriva and a chance to make the fourth round of a top-tier event on the ATP Tour for the first time.
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