The 29-year-old climbing specialist, who had finished 16th overall, has been suspended by his Saunier Duval team.
"The Saunier Duval team were notified by the International Cycling Union (UCI) that Iban Mayo had tested positive for EPO following a test on July 24 which was a rest day on the Tour de France," a team statement read.
Mayo has been suspended by the team and faces the sack if his B sample confirms the positive test.
The Tour lurched from crisis to crisis in its final week, with pre-race favourite Alexander Vinokourov - now sacked by the Astana team - testing positive for blood doping last Tuesday.
Italian rider Cristian Moreni was ejected the next day having tested positive for testosterone.
The latter's expulsion came soon after then race leader Michael Rasmussen took victory in the 16th stage of the event in the Pyrenees.
However, the Dane, whose participation had already been queried after he missed four dope tests in 18 months, was then thrown out by his Rabobank team for lying about his training whereabouts in June.
Rasmussen had said he had been in Mexico when in fact he had been sighted in Italy.
Last month Mayo was reported to have tested positive for testosterone in the Giro d'Italia. However, he was subsequently cleared by the UCI.
Previously having ridden for the Euskaltel Euskadi team, Mayo finished sixth in the Tour de France in 2003 and won Dauphine Libere race the following year.
