Recent studies investigating future warming scenarios have shown that the ocean oxygen content will continue to decrease over the coming century due to ocean warming and changes in oceanic circulation. However, significant uncertainties remain regarding the magnitude and patterns of future ocean deoxygenation. Here, we simulate ocean oxygenation with the ACCESS ESM1.5 model during two past interglacials that were warmer than the preindustrial climate, the Last Interglacial (Marine Isotope Stage (MIS) 5e, ~ 129–115 ka) and MIS 9e (~ 336–321 ka). While orbital parameters were similar during MIS 5e and MIS 9e, with lower precession, higher eccentricity and higher obliquity than pre-industrial, greenhouse gas radiative forcing was highest during MIS 9e. We find that the global ocean is overall less oxygenated in the MIS 5e and MIS 9e simulations compared to the preindustrial control run and that oxygen concentrations are more sensitive to changes in the distribution of incoming solar radiation than to differences in greenhouse gas concentrations. Large regions in the Mediterranean Sea are hypoxic in the MIS 5e simulation, and to a lesser extent in the MIS 9e simulation, due to an intensification and expansion of the African Monsoon, enhanced river run-off and resulting freshening of surface waters and stratification. Upwelling zones off the coast of North America and North Africa are weaker in both simulations compared to the preindustrial control run, leading to less primary productivity and export production. Antarctic Bottom Water is less oxygenated, while North Atlantic Deep Water and the North Pacific Ocean at intermediate depths are higher in oxygen content. All changes in oxygen concentrations are primarily caused by changes in ocean circulation and export production and secondarily by changes in temperature and solubility.