Two-time champion Kauto Star is rated "50-50" to race in the Cheltenham Gold Cup after suffering a fall on the gallops on Friday.
The Paul Nicholls-trained 12-year-old took a "pretty awful fall" under jockey Ruby Walsh at his Somerset yard.
"There's no easy way to say this but Kauto Star is only 50-50 to make the Gold Cup," said Nicholls on Betfair.
The 16 March Cheltenham showpiece was expected to be a duel between Kauto Star and defending champion Long Run.
“Even if there is the slightest doubt in our minds, then he stays at home. No question.”Kauto Star's trainer Paul Nicholls
Kauto Star's owner Clive Smith told BBC Radio 5 live: "I'm very, very concerned indeed. There is grave doubt whether we can make it. We're just hoping for the best that he makes a bit more of a recovery from this point in time.
"He will not run unless the best veterinary advice says he is up to taking part in such a serious race. There's no question the horse's welfare is paramount and we want the best future for him."
Nicholls added in his blog: "As a trainer, it is all too easy to sit on information when it comes to your horses.
"They have so many minor worries, niggles and setbacks - most of which turn out to be nothing of long-term importance - that you could be constantly updating on each of your string, to the press and the public, on a hourly, daily and weekly basis.
"But our policy at Ditcheat is always to be up front and honest about the well-being of our horses - such as the coughing scare last week - and especially so when it is a public, and once-in-a-lifetime horse, such as Kauto.
"In my opinion, the public have a right to know. In many ways, he is as much theirs, as Clive Smith's and ours.
"So I am sad to report that his participation at the Cheltenham Festival is in doubt."
Nicholls said Kauto Star was clearly sore after the fall and admitted he hoped he would be showing more improvement by now.
"Next week is crucial for the horse," added Nicholls.
"He is still cantering each day but I can assure you right now that Kauto Star won't be going anywhere near Cheltenham unless we are all convinced - Clive Smith, myself, Clifford and the team here - that he is 110%.
"Even if there is the slightest doubt in our minds, then he stays at home. No question. We will do what is best for the horse. Always have, always will. End of story.
"But one thing I think we have all learned with Kauto is never to write him off."
Walsh told Racing UK: "He's done it a few times on the track but never at home, he's probably been round that school a thousand times.
"If I knew why he'd done it you'd prevent them all falling. It's part of racing. It's not great timing but it happened.
"I've seen horses bounce back from this and win the next day. If he's right he'll run and if he's not he won't.
"I don't even want to think about what I might ride if he doesn't run."
Kauto Star looked to be in the twilight of his career at the start of the season following the defeats by Long Run in the 2010 King George and the subsequent Gold Cup in March before pulling up at Punchestown in May.
But Nicholls's charge, who won the Cheltenham Gold Cup in 2007 and 2009, hit back to beat younger rival Long Run in the prestigious Betfair Chase at Haydock in November .
And he created history when he again defeated Long Run to land a fifth King George VI Chase victory at Kempton Park on Boxing Day to set up the Cheltenham showdown.
"This is very serious," said BBC horse racing correspondent Cornelius Lysaght. "It would be a real blow to the Gold Cup - an enormous shame not just to racing but to sport in general. When champions come back and try to win again people love to see them in action and if he's not there to take on Long Run he will be sorely missed."
