The master trainer's latest success came in Sunday's Irish Derby at Curragh where High Chaparral stormed to a comfortable victory.
However the champion trainer fears if the incinerator is built, and it has already received planning permission from the local county council, it will have a detrimental effect on his horses.
O'Brien has built up the County Tipperary stable put on the map originally by his namesake Vincent O'Brien into the most successful training operation in Europe.
In an interview with the Sunday Independant newspaper O'Brien described the incinerator plan as "madness".
"If the pollution that could be caused by this incinerator causes even a fraction of a percentage difference in the horses' performance it is too much," said O'Brien.
"You win and lose races by short heads, by the tiniest of margins.
"There is no way in the wide, earthly world that anyone can say this couldn't affect the horses' performance. It will wipe us out here".
Manchester United manager Sir Alex Ferguson, part-owner of the O'Brien-trained five-time Group One winner Rock Of Gibraltar, has given his support to the campaign.
In a letter to Coolmore Stud manager Christy Grassick he said: "I am abhorred that this proposal could be allowed to proceed.
"If it is constructed I will be very slow to continue my connection with the area," added Ferguson.
National By-Products Ltd, the company behind the incinerator, claim the new plant will burn only meat and animal bonemeal, and would be completely safe from a health perspective.
Tackled on the matter after his Irish Derby success O'Brien said that if he was forced to move he would consider America as a new base camp.
"There are a lot of options - Coolmore has a big operation in America and that is definitely an option," he said.