The middle Miocene climate transition (MMCT), likely triggered by a decrease in atmospheric CO2 concentration and changes in the Earth's orbital configuration, entailed major expansion of the Antarctic ice-sheet and cooling of the global ocean at ~15–13 Ma. By comparing simulations that use boundary conditions representative of 15 and 13 Ma, we assess the response of ocean temperatures and deep ocean circulation to atmospheric CO2 drawdown (from 400 to 200 ppmv) and Antarctic ice-sheet expansion (43 m of sea-level equivalent) during the MMCT by means of the Community Climate System Model version 3. The model simulates a decrease in mean global sea-surface temperature by 1.6 °C across the transition. Individual forcing experiments reveal that surface cooling is fully attributable to the CO2 drop, whereas expansion of the Antarctic ice-sheet tends to cause a slight global warming of the upper ocean. At depth, modelled ocean temperatures decrease by 1.5–2 °C across the MMCT in most regions. While the CO2 effect dominates deep-ocean cooling, about 25–30% is attributable to the expansion of the Antarctic ice-sheet.In the convection regions of the Southern Ocean, the CO2 drawdown causes an increase in salinity through sea ice formation and changes in the precipitation-evaporation balance. This increase in salinity, together with a decrease in surface temperatures, translates into an intensification in Antarctic Bottom Water formation that cools the deep ocean. The contribution of the Antarctic ice-sheet expansion to bottom and deep water cooling occurs through an increase in the surface heat flux from the ocean to the atmosphere, which is linked to intensified cold surface winds blowing off the Antarctic continent.This study suggests that the magnitude of cooling of deep waters across the MMCT inferred from proxy records can be explained by the combined effects of the CO2 decrease and Antarctic ice-sheet expansion. Our surface cooling estimates are generally lower than those indicated by proxies.