We use an earth system model to simulate ocean oxygen during two past warm periods, the Last Interglacial (∼ 129–115 ka) and Marine Isotope Stage (MIS) 9e (∼ 336–321 ka). The global ocean is overall less oxygenated compared to the preindustrial simulation. Large regions in the Mediterranean Sea are oxygen deprived in the Last Interglacial simulation, and to a lesser extent in the MIS 9e simulation, due to an intensification and expansion of the African monsoon and enhanced river runoff.