Danedream has been officially scratched from the Prix de l'Arc de Triomphe at Longchamp on Sunday.
News broke on Monday evening that Cologne racecourse, where Peter Schiergen's fantastic mare is stabled, was to be dramatically placed into quarantine.
The German track has been shut down for three months after a horse tested positive for equine infectious anemia (EIA), also known as swamp fever, on Monday night.
All horses based at Cologne cannot leave the racecourse, including Danedream, a brilliant winner of the Longchamp feature 12 months ago.
France Galop's media manager Julien Pescatore said: "There is a quarantine period of 90 days, and for that reason Danedream will not be able to run in the Arc.
"It is really sad that she will not be able to run, but there is nothing we can do about it."
Eighteen horses remain in contention, while Saonois is expected to be supplemented for the race at a cost of €100,000 on Thursday.
The timing of the closure of Cologne racecourse could not have been worse for Danedream's connections.
Patrick Barbe, racing manager for her part-owner Teruya Yoshida, said on Tuesday morning: "The quarantine is round the race track in Cologne and nothing can come in and out of there for three months.
"That situation at the moment is final and binding.
"If the race was in two weeks they might have found a solution, but with time being so short to the deadline for the race it has proved too difficult."
Japanese challenger Orfevre, winner of the Prix Foy last month, was also among those left in Europe's premier middle-distance race following the latest scratchings stage.
Nathaniel, runner-up to Danedream in the King George VI And Queen Elizabeth Stakes at Ascot in July, similarly remains on course for Paris.
Camelot's trainer Aidan O'Brien also has Imperial Monarch, St Nicholas Abbey, Ernest Hemingway and Robin Hood.
Andre Fabre, who already has seven Arc victories to his name, has two representatives in Prix Foy runner-up Meandre and Masterstroke, owned by Godolphin's French section.
The Aga Khan's Shareta, who was second to Danedream 12 months ago, showed her well-being when winning the Prix Vermeille over the course and distance recently.
Her trainer Alain de Royer-Dupre also has Reliable Man in the mix.
Michael Stoute's Sea Moon, carrying the Frankel colours of owner Khalid Abdullah, is also in the shake-up.
The others are Mikhail Glinka, Aventino, Haya Landa, Solemia, Kesampour and Yellow And Green.
Best odds as of 11.15am on Tuesday, 2 October:
Orfevre 3-1, Nathaniel 4-1, Camelot 5-1, Shareta 8-1, Saonois* 10-1, Masterstroke 12-1, St Nicholas Abbey 12-1, Sea Moon 16-1, Meandre 16-1, Imperial Monarch 20-1, Yellow And Green 33-1, Solemia 40-1, Reliable Man 50-1, Kesampour 50-1, Mikhail Glinka 66-1, Ernest Hemingway 100-1, Haya Landa 150-1, Aventino 200-1, Robin Hood 250-1.
* Needs to be be supplemented for the race