Leading Qipco 1000 Guineas hope Chriselliam has been put down after failing to recover from a foot infection.
The Charlie Hills-trained daughter of Iffraaj triumphed in the Fillies' Mile at Ascot last season from the classy Rizeena, before connections took the brave decision to send her to the Breeders' Cup.
And they were rewarded at Santa Anita when she streaked clear under Richard Hughes to win the Juvenile Fillies Turf in tremendous style.
Former champion jockey Willie Carson was one of her owners along with music mogul Chris Wright, who tweeted: "RIP Chriselliam. A true champion on both sides of the Atlantic. Only the good die young. By far the best we have ever had or will ever have."
Last month Hills revealed that Chriselliam had been suffering with a poisoned foot and was recovering at the Equine Hospital in Lambourn before being moved to Newmarket.
At the time Hills was confident she would be able to continue her racing career.
Hills said: "It's a shocker.
"Basically she split her shoe and we thought we had it under control but she took a bad turn and it got reinfected.
"The antibiotics weren't working and it spread to her pedal bone.
"The vets tried everything. It's been a long month for us all.
"She'd been a wonderful patient and never lost her appetite. It's very sad for everyone involved and I'd like to thank all the vets who tried to save her.
"Unbelievably the trophy for the Breeders' Cup only arrived today."
A dual Group One winner, Chriselliam amassed nearly £500,000 in just six races.