Belfast doctor O'Neill's decision was followed by the resignations of three other doctors who are connected to the Northern Ireland area council for the board.
A cyst was found near McCullough's brain two years ago when he was set to box in Belfast and that led the board to refuse him permission to fight.
"I feel that ethically and morally I can longer be part of boxing," said O'Neill.
"I will not discuss individual cases but my views are quite clear.
"I have been working for 20 years with the council and I will miss boxing as I have made many friends in the sport.
"It is unfortunate that I have had to make this decision but I feel I have no alternative."
Northern Ireland area council secretary John Campbell added: "I can understand why George has done this.
"It is on a matter of principle but I wish that he would reconsider.
"George has brought a lot of safety to boxing and we can't afford to lose people of his stature. I wish he would stay on to help the boxers."
Cheryl McCullough, Wayne's wife and manager, told the BBC that O'Neill could have voiced any fears he may have had about the Ulster boxer sooner than this.
"Myself and Wayne are not sure what the facts of this story are at the minute as we only know what we have read in the newspapers," Cheryl said from their family home in Las Vegas.
"The press are assuming that George O'Neill has resigned over Wayne and if that is the case then he should come out and say so.
"I have had no correspondance with George since about October 2000.
"Everything was on his desk the Wednesday before Wayne was granted his licence.
"So he should have aired any opinion he had on the matter then rather than waiting until now and casting a shadow over this fantastic time in Wayne's career."