We investigated the physical processes underlying the degradation of poly(3-hexyl-thiophene):phenyl-C61-butyric acid methyl ester (P3HT:PCBM) photovoltaics under harsh environmental conditions during a 70-70-70 test (70% humidity at 70 °C from 0 to 70 h) using a variety of analytical techniques aimed at monitoring moisture incorporation. While the total oxygen content did not significantly increase during the test, a limited fraction of oxygen forms paramagnetic centers in P3HT, PCBM and, more limitedly, P3HT:PCBM heterojunctions. A strong correlation exists between the density of paramagnetic centers and the decay in the AM 1.5 photoconversion efficiency of the devices.