Paula Radcliffe has pulled out of this year's London Marathon on 23 April with the same foot injury which forced her to miss the Commonwealth Games.
Radcliffe has not raced competitively since November
The 32-year-old world marathon champion has previously won the event three times - in 2002, 2003 and 2005.
"I am really disappointed to have to miss this year's event," Radcliffe said. "I have to accept that the injury needs a short period of total rest."
Britain's top male distance runner Jon Brown has also pulled out.
Radcliffe broke the women's only world record on two occasions in London - in 2002 (2 hours 18 minutes 56 seconds) and 2005 (2:17:42), and also the mixed world record (2:15:25) in 2003.
She returned early from her training base in Albuquerque, New Mexico, 10 days ago for expert treatment from top German surgeon Hans Muller-Wohlfahrt in Munich.
But the foot injury - a knock-on effect after she bruised the underside of a toe on a training run last December - means she may have to wait until August before racing again - in defence of her European Championship 10,000m title.
She could then contest an autumn marathon, with Chicago and New York obvious contenders.
"The Flora London Marathon is something that is extremely important to me, and I have done everything possible to resolve the problem and get to the start line," Radcliffe added.
"But now I have to focus on moving on from this and my future."
Race director David Bedford acknowledged that once Radcliffe withdrew from the Commonwealth Games, her participation in London was always in doubt.
"To race when less than fully fit is simply not the Paula we know and could jeopardise her form for some time," he said.
"We fully understand that this is the right decision and look forward to welcoming Paula back in the future.
"The Flora London Marathon will still serve up two great races on 23 April and, if anything, the women's race will be all the more intriguing."
Brown, meanwhile, has been suffering from a foot problem recently which has left him "way behind" in his training preparations.
"I feel like I have only done two-thirds of the training needed, and I know this isn't enough for London as I cannot expect to perform to the level I feel I should," he said.
"This is disappointing for me especially as this year's race looks to be such a great one."
The men's field boasts Kenya's world record holder Paul Tergat, Ethiopian legend Haile Gebrselassie, Italy's Olympic champion Stefano Baldini and last year's winner, Kenyan Martin Lel.
Organisers also announced on Monday the addition of 1999 London winner Abdelkader El Mouaziz to the field.
El Mouaziz has competed in London eight times and broken 2:10 on each occasion. He finished fourth in 2005 in 2:09:03.