Trainer Aidan O'Brien is hopeful St Mark's Basilica will return to action in time to run in next month's Irish Champion Stakes.
The Siyouni colt has carried all before him in three previous starts this season, completing a Classic double with victories in the French 2000 Guineas and French Derby before producing a brilliant display in the Coral-Eclipse at Sandown last month.
St Mark's Basilica was odds-on across the board to continue his winning streak on the opening afternoon of York's Ebor Festival, but will not make the trip across the Irish Sea after suffering a setback.
O'Brien said: "Yesterday (Sunday) morning he lost a front shoe and it came back and hit his hind leg - his near-hind joint.
"We didn't think a lot of it, but this morning there was a little bit of swelling in it - and when we took bloods off him, his bloods came back and it was a little bit infected.
"We were a bit taken aback when we saw it this morning, but when we did the bloods then we didn't have any choice as he needs to go on antibiotics and the antibiotics that he's going to go on obviously he couldn't run on.
"Hopefully we'll be back on target towards the end of this week and if we are, we'll be able to train him for the Irish Champion."
In St Mark's Basilica's absence, O'Brien will instead rely on dual Classic-winning filly Love in the Juddmonte International.
The Ballydoyle handler had planned on sending the daughter of Galileo to France this weekend for the Prix Jean Romanet, but she will now bid to play the role of super-sub on the Knavesmire.
"It's four or five days earlier than we'd planned for her - the plan was to go for the Romanet on Sunday," O'Brien added.
"When St Mark's came out, we decided we'd let her run here instead."
Love made a successful start to the campaign in the Prince of Wales's Stakes at Royal Ascot in June, but suffered her first defeat since the autumn of 2019 when only third in the King George at Ascot on her latest appearance.
The daughter of Galileo will renew rivalry with John and Thady Gosden's King George runner-up Mishriff, who had previously finished third behind St Mark's Basilica in the Eclipse.
Andrew Balding runs stable star Alcohol Free, while William Haggas saddles both Mohaafeth and Alenquer.
Alcohol Free tests the water over a mile and a quarter for the first time after enjoying two Group One wins over a mile in the the Coronation Stakes and the Sussex Stakes.
Mohaafeth was beaten for the first time this season when third in the York Stakes over the course and distance last month, while Alenquer drops back in distance after placing third in the Grand Prix de Paris over a mile and a half.
The field is completed by Kevin Ryan's Juan Elcano and the Jim Bolger-trained Mac Swiney, winner of the Irish 2,000 Guineas.