Motivated by the use of atmospheric O2/N2 to determine CO2 sinks under the assumption of negligible interannual variability in air-sea O2 fluxes, we examine interannual fluctuations of the global air-sea flux of O2 during the period 1980--1998 using a global ocean circulation and biogeochemistry model along with an atmospheric transport model. It is found that both the El Ni¿o/Southern Oscillation (ENSO) cycle and wintertime convection in the North Atlantic are primary drivers of global air-sea oxygen flux interannual variability. Model estimated extremes of O2 flux variability are -70/+100 ¿ 1012 mol/yr (Tmol/yr), where positive fluxes are to the atmosphere. O2/N2 variability could cause an up to ¿1.0 PgC/yr error in estimates of interannual variability in land and ocean CO2 sinks derived from atmospheric O2/N2 observations.