Enable will be out of action until August at the earliest after suffering a setback, connections have anounced.
John Gosden's brilliant filly enjoyed a fantastic campaign in 2017, winning six of her seven starts including five consecutive Group One triumphs.
She has not been seen on a racecourse since claiming Prix de l'Arc de Triomphe glory at Chantilly last October, but had been pencilled in to make her reappearance in the Coronation Cup at Epsom on June 1.
However, she will now miss the first part of the season through injury.
Teddy Grimthorpe, racing manager to owner Khalid Abdullah, said in a statement to Press Association Sport: "Enable has met with a setback in training. She has some filling in her knee which is being fully investigated."
Connections are hopeful Enable will run again before defending her Arc crown in Paris.
Grimthorpe added: "The advice that we have is, that given reasonable circumstances, she should be ready to run in August as a preparation for the Prix de l'Arc de Triomphe."
Having burst on to the scene at Epsom with her five-length win in the Investec Oaks, Enable repeated the dose in the Darley-sponsored Irish Oaks, in even more impressive fashion.
Connections then took the bold step to run her against the older colts in the King George VI And Queen Elizabeth Stakes and they were dealt with in much the same way.
Group One winners like Ulysses and Highland Reel did not see which way she went and officials at Ascot would no doubt have been hoping she would grace the race again in July.
A clash with stablemate Cracksman would have been one for the ages, with Frankie Dettori already agonising over the decision of which superstar to ride. Now he will have until October to choose.
"The King George is still so far ahead that you wouldn't be realistically thinking about it anyway. That's racing, you don't really believe things until you see them in the stalls," said Nick Smith, Ascot's director of communications.
"Saxon Warrior (2000 Guineas winner) could be a possibility now, you would have thought - him up against Cracksman would be pretty exciting. Then you've the other older horses like Defoe and Capri. It's always a shame when you lose one, but there is such strength in depth this year.
"To say Lah Ti Dar (another stablemate of Enable) has a long way to go is an understatement, but she is certainly on the right road and it seems to be a recent trend for Oaks winners to run in the King George, what with Taghrooda and Enable.
"Hopefully we'll see Enable on the track later in the year."
Enable remains 11/4 favourite with Sky Bet for the Arc, but she's closely followed in the betting by stablemate Cracksman, who is 3/1.
Press Association Sport takes a look at those horses most likely to benefit from Enable's absence:
A stablemate of Enable, their potential clash in the King George VI And Queen Elizabeth Stakes will not now materialise and it looks like the earliest they could meet is in the Prix de l'Arc de Triomphe. In Enable's absence Cracksman is likely to go off at prohibitive odds for the mid-summer highlight at Ascot and while Frankie Dettori will be disappointed with the news of her injury, it at least means he does not have to pick between the pair before October.
A dual Classic winner last year, in the Irish Derby and St Leger, the style of his comeback success at Naas suggests he will win plenty more races before a stud career beckons. While it would have needed him to improve considerably to beat Enable, the fact she will now be absent from both the Tatersalls Gold Cup at the Curragh and the Coronation Cup at Epsom, which was looking like being her comeback, means more opportunities for Capri to add another Group One to his record.
Another stable companion of Enable. She may have a long way to go yet to fill Enable's shoes, but this time last year Enable was still to burst on to the scene and Lah Ti Dar is already a Listed winner. She is one of the favourites for the Oaks and were she to win at Epsom there is every possibility she could mop up the fillies' races in the middle of the summer, the Yorkshire Oaks and the like.
Although put in his place in the St Leger, he has subsequently proved that was not his true running with two very easy Group-race wins this season. He has now won seven of his last eight races and is surely a Group One winner in waiting. Where that may be is the question, but the Tattersalls Gold Cup was not ruled out after his easy Newmarket win at the weekend and connections may well strike while the iron is hot.
The general consensus before his impressive 2000 Guineas success was that Saxon Warrior would improve markedly for the run, given how much he had grown over the winter. If that is the case then he looks set to clear up in his own generation, with the Investec Derby next for him. After that, the Triple Crown will loom large and Coolmore will surely take it on, but the King George may well be too good an opportunity to turn down given the weight-for-age allowance.