The former was due to run in Saturday’s Long Walk Hurdle at Ascot, while Al Ferof was being prepared for an assault at the King George VI Chase at Kempton on St Stephen’s Day.
Nicholls told Betfair: “At evening stables tonight, we discovered a problem with both Big Buck’s and Al Ferof.
“I am not in a position to go into great detail at this point, but I can confirm that Big Buck’s will not be taking up his engagement at Ascot on Saturday and Al Ferof will not be running in the King George.”
Big Buck’s’ owner Andy Stewart said the remarkable nine-year-old, who has won his last 18 races, has suffered a leg injury and would not defend his crown in the Ladbrokes World Hurdle at the Cheltenham Festival next March.
He said: “He didn’t do it (sustain the injury) on the gallops.
“He was a little bit anxious in one of his legs at evening stables and after Clifford (Baker, Nicholls‘ head lad) and the vet inspected him, we decided to draw stumps.
“He’ll not be running on Saturday and he won’t be trying to win a fifth World Hurdle in March.
“I’m a little bit gutted, but no-one has died and the horse is perfectly well.
“When the horses come back in at the end of July we shall reassess the situation.
“If he hasn’t got that zest and sparkle, he will be retired.”
Al Ferof, a fine winner of the Paddy Power Gold Cup at Cheltenham in November, has damaged a tendon and will miss the rest of the season, said owner John Hales.
“We were all set for the King George, but things like this are part of the game,” Hales said.
“We don’t know how he got the tendon injury, but that’s him out for the season.
“We’ll obviously get him reassessed by the vet, but you can bet your life the King George and then the Gold Cup will be the plan in 12 months‘ time.
“He’s still a youngster and has age on his side.”
Nicholls later tweeted neither Big Buck’s nor Al Ferof had sustained career-threatening injuries and that the pair will “both will be back”.