Wuheida, Godolphin's unbeaten G1 winner, has been ruled out of the first two fillies' Classics after sustaining a stress fracture to her right hind leg.
She is expected to be on the sidelines for the remainder of Spring and most of Summer -- ruling her out of the 1,000 Guineas at Newmarket on May 7 and the Oaks at Epsom on June 2.
"It is very disappointing for all of us at Godolphin," trainer Charlie Appleby said.
"She had been doing so well in her work at home, and we were really looking forward to the Guineas.
"The recuperation period is six to eight weeks, so she misses some important races. But if she progresses well in her recovery, we should be looking to having her back, running again, in the second half of the season.
"She is a high-class filly, as she showed so impressively at Chantilly last Autumn," he added.
Wuheida, a daughter of Dubawi, landed the G1 Prix Marcel Boussac on October 2, which was a big step up from the fillies' maiden she won at Newmarket on her previous start.