Because oxygen cannot be fully eliminated from organic solar cells, the occurrence of oxidative photo-degradation of the device in operating conditions has to be considered. Polyphenylene-vinylene-based photovoltaic devices have a short lifetime that currently limits their applications. In this article, we focus on various transient species that are potentially involved in the initiation step of the photo-oxidation of poly[2-methoxy-5-(30,70- dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV). The role of the transient species was investigated by a combination of quenching and sensitization experiments. Complementary information was obtained by transient absorption spectroscopy. Results evidenced the fact that 1O2 was not the principal reactive intermediate involved in the photo-oxidation of MDMO-PPV. This result was in contradiction with previous reports. It was shown that the MDMO-PPV=p radical cation was generated after excitation. The presence of oxygen and the photo-aging favored the formation of the radical cation, suggesting that oxygen and photoproducts act as electron acceptors. The charged radicals formed are likely to evolve and give radicals that initiate the oxidation of the polymer by abstraction of the labile hydrogen in a position of the ether function and by addition on the double bonds.