Michael Vaughan will undergo a fourth knee operation on Monday which will cast major doubt on his participation in the Ashes series later this year.
Vaughan had been playing for Yorkshire to get himself fit
The England captain has opted to have more surgery to repair damage to cartilage in his right knee.
The 31-year-old batsman is expected to be sidelined for between four and six months, leaving him with an uphill battle to be fit for Australia.
The first Test of the five-match series starts in Brisbane on 23 November.
Vaughan will have the surgery at an undisclosed hospital in the United Kingdom.
Dr Peter Gregory, the England and Wales Cricket Board's chief medical officer, said: "Michael worked extremely hard with the support of the Yorkshire medical staff to strengthen the knee to the point where he was able to begin playing again.
"However, he has still been experiencing some discomfort in the knee and further surgery is necessary if he is to regain the level of fitness required for international cricket.
"Our priority now is to safeguard Michael's long-term interests and ensure that he can resume his playing career.
"He will have our full support and we will be closely monitoring his progress in conjunction with the staff at Yorkshire who will supervise his day-to-day rehabilitation programme."
The news will come as a desperate disappointment for Vaughan, who played such a leading role in guiding England to their first series win over Australia since 1986-87 last summer.
1999 Misses 3rd Test in South Africa with finger injury
2000 Misses home series against Zimbabwe with broken finger
2000 Strains calf muscle during tour to Pakistan
2001 Misses home Ashes series after surgery on left knee
2004 Misses first Test against New Zealand after twisting left knee
2005 Twists right knee while running between wickets in Pakistan and misses opening Test
March 2006 Flies home from tour to India after recurrence of knee trouble
June 2006 Decides to undergo further surgery on knee
An ECB spokesman told BBC Sport: "The doctor's statement does not even mention the Ashes because we do not want to put pressure on Michael or the medical staff."
Vaughan has not played for England since the tour of India at the beginning of the year.
He first had surgery in 2002 and then again late last year after coming home early from the tour of Pakistan.
Vaughan declared himself fit for the tour of India in the spring but broke down during a warm-up match and had to fly home.
After resting, he started his rehabilitation and had been playing for Yorkshire but suffered a recurrence of his long-standing problems during the County Championship match against Sussex at Arundel last week.
England coach Duncan Fletcher admitted it was difficult to contemplate being without his captain.
"I really feel for Michael. He is so keen and passionate about playing for England and really wants to get out there and score runs for us again," he said.
"I feel really frustrated for him because he worked really hard to get playing again. There was no messing around for him, he did everything properly and it's desperately bad luck that he now has to have an operation.
"He just loves batting and scoring runs and to have that taken away from him must be very hard. He is desperate to get back playing again and we all are hoping the operation is successful and he can return for England."
The England hierarchy added that there would be no decision about a captain for the winter until much nearer the time, when more about Vaughan's situation is known .
Spinner Ashley Giles, meanwhile, has undergone a second hip operation after flying to Colorado in America to see a colleague of Dr Richard Steadman, the knee and shoulder specialist who operated on Simon Jones.