The reigning world 100m bronze medallist and former world record holder had pulled out of recent meetings in Stockholm, London, Paris and Zurich due to injuries to his groin, back and hamstring.
His agent Paul Doyle said fitness issues coupled with the timing of the Commonwealth Games almost certainly rules out Powell defending his 100m gold in Delhi.
"A final decision is imminent, but it's looking extremely unlikely at best that Asafa will be in India," Doyle was quoted as saying by the 'Daily Mail'.
Other stars who have already announced their non-participation are Paula Radcliffe, world and European heptathlon champion Jessica Ennis, athletes Jenny Meadows and Natasha Danvers.
Powell suffered back and hamstring injuries earlier this year and pulled out of a sprint showdown with Tyson Gay and Bolt in Stockholm.
"The timing couldn't be much worse for Asafa," said Doyle.
"For him, just as for Usain, the next two-year cycle means everything and he doesn't want anything, such as his pre-season being put back, or his injuries flaring up again, to affect this," he added.
Powell's withdrawl comes as another blow to the Delhi Games organisers, who are already battling allegations of financial irregularities.