Deep water formation (DWF) in the North Western Mediterranean (NWMed) is a key feature of Mediterranean overturning circulation. DWF changes under global warming may have an impact on the Mediterranean biogeochemistry and marine ecosystem. Here we analyze the deep convection in the Gulf of Lions (GoL) in a changing climate using a regional climate system model with a horizontal resolution high enough to represent DWF. We find that under the RCP8.5 scenario the NWMed DWF collapses by 2040–2050, leading to a 92% shoaling in the winter mixed layer by the end of the century. The collapse is related to a strengthening of the vertical stratification in the GoL caused by changes in properties of Modified Atlantic Water and Levantine Intermediate Water, being their relative contribution to the increase of the stratification 57.8% and 42.2%, respectively. The stratification changes also alter the Mediterranean overturning circulation and the exchange with the Atlantic.