Abstract Diffusion coefficients for oxygen and hydrogen were determined from a series of natural uraninite–H 2 O experiments between 50 and 700 °C. Under hydrous conditions there are two diffusion mechanisms: (1) an initial extremely fast-path diffusion mechanism that overprinted the oxygen isotopic composition of the entire crystals regardless of temperature and (2) a slower volume-diffusive mechanism dominated by defect clusters that displace or eject nearest neighbor oxygen atoms to form two interstitial sites and two partial vacancies, and by vacancy migration. Using the volume diffusion coefficients in the temperature range of 400–600 °C, diffusion coefficients for oxygen can be represented by D = 1.90e −5 exp (−123,382 J/RT) cm 2 /s and for temperatures between 100 and 300 °C the diffusion coefficients can be represented by D = 1.95e −10 exp (−62484 J/RT) cm 2 /s, where the activation energies for uraninite are 123.4 and 62.5 kJ/mol, respectively. Hydrogen diffusion in uraninite appears to be controlled by similar mechanisms as oxygen. Using the volume diffusion coefficients for temperatures between 50 and 700 °C, diffusion coefficients for hydrogen can be represented by D = 9.28e −6 exp (−156,528 J/RT) cm 2 /s for temperatures between 450 and 700 °C and D = 1.39e −14 exp (−34518 J/RT) cm 2 /s for temperatures between 50 and 400 °C, where the activation energies for uraninite are 156.5 and 34.5 kJ/mol, respectively. Results from these new experiments have implications for isotopic exchange during natural UO 2 –water interactions. The exceptionally low δ 18 O values of natural uraninites (i.e. − 32‰ to −19.5‰) from unconformity-type uranium deposits in Saskatchewan, in conjunction with theoretical and experimental uraninite–water and UO 3 –water fractionation factors, suggest that primary uranium mineralization is not in oxygen isotopic equilibrium with coeval clay and silicate minerals. The low δ 18 O values have been interpreted as resulting from the low temperature overprinting of primary uranium mineralization in the presence of relatively modern meteoric fluids having δ 18 O values of ca. −18‰, despite petrographic and U–Pb isotope data that indicate limited alteration. Our data show that the anomalously low oxygen isotopic composition of the uraninite from the Athabasca Basin can be due to meteoric water overprinting under reducing conditions, and meteoric water or groundwater can significantly affect the oxygen isotopic composition of spent nuclear fuel in a geologic repository, with minimal change to the chemical composition or texture. Moreover, the rather fast oxygen and hydrogen diffusion coefficients for uraninite, especially at low temperatures, suggest that oxygen and hydrogen diffusion may impart characteristic isotopic signals that can be used to track the route of fissile material.