Ocean carbon uptake and oxygen content estimates over the past decades suggest that the anthropogenic carbon sink has changed and that the oxygen concentration in the ocean interior has decreased. Although these detected changes appear consistent with those expected from anthropogenic forced climate change, large uncertainties remain in the contribution of natural variability. Using century-long simulations (500-1000 years) of unforced natural variability from six Earth System Models (ESMs), we examine the internally driven natural variability of carbon and oxygen fluxes from interannual to multidecadal time scales. The intensity of natural variability differs between the ESMs, in particular, decadal variability locally accounts for 10-50% of the total variance. Although the variability is higher in all regions with strong climate modes (North Atlantic, North Pacific, etc.), we find that only the Southern Ocean and the tropical Pacific significantly modulate the global fluxes. On (multi)decadal time scales, deep convective events along the Antarctic shelf drive the global fluxes variability by transporting deep carbon-rich/oxygen-depleted waters to the surface and by reducing the sea-ice coverage. On interannual time scales, the global flux is modulated by (1) variations of the upwelling of circumpolar deep waters associated with the southern annular mode in the subpolar Southern Ocean and (2) variations of the equatorial/costal upwelling combined with changes in the solubility-driven fluxes in response to El Niño Southern Oscillation (ENSO) in the tropical Pacific. We discuss the challenges of measuring and detecting long-term trends from a few decade-long records influenced by internal variability. © 2014. American Geophysical Union. All Rights Reserved.