SummarySecular decreases in dissolved oxygen concentration have been observed within the tropical Oxygen Minimum Zones (OMZs) and at mid-to high latitudes over the last ~ 50 years. Earth System Model (ESM) projections indicate that a reduction in the oxygen inventory of the global ocean, termed ocean deoxygenation, is a likely consequence of on-going anthropogenic warming. Current models are, however, unable to consistently reproduce the observed trends and variability of recent decades, particularly within the established tropical OMZs. Here we conduct a series of targeted hindcast model simulations using a state-of-the-art global ocean biogeochemistry model in order to explore and review biases in model distributions of oceanic oxygen. We show that the largest magnitude of uncertainty is entrained into ocean oxygen response patterns due to model parameterisation of pCO2-sensitive C:N ratios in carbon fixation and imposed atmospheric forcing data. Inclusion of a pCO2-sensitive C:N ratio drives historical oxygen depletion within the ocean interior due to increased organic carbon export and subsequent remineralisation. Atmospheric forcing is shown to influence simulated interannual variability in ocean oxygen, particularly due to differences in imposed variability of wind stress and heat fluxes.