The 25-year-old had was taken ill in Ethiopia in January and has struggled since then, managing only an 11th-placed finish in a Diamond League mile race at Eugene in the United States on June 1 in a rare outing.
His manager Mohamed Azzoug told the El Watan website that Makhloufi had not recovered sufficiently to take part in the Aug. 10-18 world championships in Moscow, although Algerian athletics officials said they had not been officially notified of his withdrawal.
Makhloufi was a controversial figure at the London Olympics, where he was disqualified from the Games by the IAAF for not making a "bona fide effort" after dropping out early in his 800m heat to preserve his energy for the 1,500 metres final, for which he had already qualified.
He then produced a doctor's certificate saying he had suffered an unspecific injury and he was duly re-instated and went on to take the 1,500 gold having improved his personal best over the distance by more than two seconds during the year.
Women's 1,500 metres champion, Asli Cakir Alptekin of Turkey, will also miss the world championships after failing a drugs test.
Leading sprinters Tyson Gay of the United States and Jamaica's Asafa Powell are also out after drugs test failures while world 100m champion Yohan Blake will not defend his title because of a hamstring strain.
Kenya's world and Olympic 800m champion David Rudisha is also absent with a knee injury.