We analyze the climate change signal in the Mediterranean Sea using the regionally coupled model REMO-OASIS-MPIOM (ROM; abbreviated from the regional atmosphere model, the OASIS3 coupler and the Max Planck Institute Ocean Model). The ROM oceanic component is global with regionally high horizontal resolution in the Mediterranean Sea so that the water exchanges with the adjacent North Atlantic and Black Sea are explicitly simulated. Simulations forced by ERA-Interim show an accurate representation of the present Mediterranean climate. Our analysis of the RCP8.5 (representative concentration pathway) scenario using the Max Planck Institute Earth System Model shows that the Mediterranean waters will be warmer and saltier throughout most of the basin by the end of this century. In the upper ocean layer, temperature is projected to have a mean increase of 2.7 °C, while the mean salinity will increase by 0.2 psu, presenting a decreasing trend in the western Mediterranean in contrast to the rest of the basin. The warming initially takes place at the surface and propagates gradually to deeper layers. Hydrographic changes have an impact on intermediate water characteristics, potentially affecting the Mediterranean thermohaline circulation in the future.