Leading Irish contender In Compliance is "likely" to miss the Totesport Cheltenham Gold Cup on 16 March.
In Compliance is rated highly by trainer O'Brien
The seven-year-old horse was a 9-1 chance with the sponsors, but has not raced since beating last season's champion War Of Attrition in December.
Naas-based trainer Michael O'Brien said: "I've got to confirm it with the owner, but he's more than likely not going to go.
"I'm not that happy with him. He doesn't seem to be firing."
O'Brien said his stable star could run next at the Punchestown Festival in April.
At one stage, In Compliance was considered one of the few horses capable of seriously challenging Gold Cup favourite Kauto Star.
More than £1m has been traded on the horse through the betting exchange Betfair, but his odds there drifted to 50-1 after O'Brien's comments.
The last two Gold Cups have gone back to Ireland with victories for Kicking King and War of Attrition, who led home a gaelic 1-2-3 on St Patrick's Day.
But Kicking King is injured and War of Attrition prefers drier conditions, and goes into Cheltenham after three defeats on testing ground.
Last year's runner-up Hedgehunter is an absentee, while the third Forget The Past may run in the shorter Ryanair Chase at Cheltenham instead.
That leaves current 25-1 shot Beef or Salmon as the next most likely Irish candidate.
He is a prolific performer in his homeland on soft ground, but has never won in England and has failed to make the first three in four Gold Cup attempts.