The horse's trainer, Doug O'Neill, made the announcement on the Dan Patrick Show Friday morning.
O'Neill seemed to indicate that "I'll Have Another" had been injured in some way. The nature of the injury was not immediately clear, KTLA-TV reported.
When asked if the horse has competed in his last race, O'Neill responded: "If I had to wager, I'd say yes."
The New York Racing Association has called a 1:00 p.m. ET news conference on the matter.
The 144th running of the Belmont Stakes is at 4:30 p.m. ET this Saturday.