Imperial Commander could be targeted at the John Smith's Grand National on April 6 after being ruled out of the Betfred Cheltenham Gold Cup.
A lung infection has put paid to the dream of the 12-year-old attempting to regain the blue riband prize of jumps racing on Friday week.
Trainer Nigel Twiston-Davies was convinced Imperial Commander was back to the same sort of form which saw him defeat Denman and Kauto Star in the 2010 renewal.
Having pulled up with a broken blood vessel the following year, he missed a whole season but came back at Cheltenham in January with a fine run when only narrowly denied by Cape Tribulation in the Argento Chase.
"He's got a lung infection so he won't be going to Cheltenham – that's that," said Twiston-Davies.
"What can you do – it's an absolute sickener but they are very delicate creatures.
"I'm sure he's still as good as ever, he's been in great form, but you can't rush them.
"Hopefully he'll be okay for Liverpool," he added.
Paul Costello, syndicate manager for owners Our Friends In The North, said: "He worked (Tuesday morning) and he was not right.
"With it being this close to the Festival we didn't want to take any chances.
"His safety and well-being are obviously paramount so we had to give it a miss.
"It's a desperate shame as we were expecting a big run from him – he's definitely got it in him.
"Older horses can be susceptible to more little problems than younger horses, but I think this has just been a bit of bad luck that could have happened at any time."
Imperial Commander was given 11st 6lb in the National and the owners may consider that along with other major races later in the spring.
"He's got an entry in the National, and he would have a nice weight, so we wouldn't close the door on that just yet," commented Costello.
"I know it (the National) has been mentioned, but it's maybe just as likely we'll look at the Betfred Bowl or maybe even Punchestown.
"It would be too soon to look too far ahead, but hopefully we'll have him back, fighting fit, in the spring."
Imperial Commander's regular jockey Paddy Brennan would be happy to take the National as a consolation prize.
"He'll never run in a Gold Cup again, that's the bottom line," he said. "But if he wins a Grand National, I won't be complaining."