The Godolphin colt was due to tackle the final leg of the US Triple Crown Series in New York this weekend but has picked up an infection.
Godolphin announced on Twitter: "Unfortunately Rebel's Romance will not be declared for this Saturday's G1 Belmont Stakes due to an infection in his hind leg.
"We hope this is only a minor setback and we look forward to seeing him back on the racecourse in the near future."
The Belmont would have been Rebel's Romance's first appearance since he beat Panadol by five and a half lengths at Meydan in March.
Mike Smith had been booked for the ride in New York, where trainer Charlie Appleby has a team of four horses for the Belmont Racing Festival.
Godolphin will still be represented in the US Classic with the Brad Cox-trained probable favourite Essential Quality taking his chance after finishing fourth in the Kentucky Derby.