Here, we analyze future projections of cyclone activity in the Mediterranean region at the end of the twenty-first century based on an ensemble of state-of-the-art fully-coupled Regional Climate System Models (RCSMs) from the Med-CORDEX initiative under the Representative Concentration Pathway (RCP) 8.5. Despite some noticeable biases, all the RCSMs capture spatial patterns and cyclone activity key characteristics in the region and thus all of them can be considered as plausible representations of the future evolution of Mediterranean cyclones. In general, the RCSMs show at the end of the twenty-first century a decrease in the number and an overall weakening of cyclones moving across the Mediterranean. Five out of seven RCSMs simulate also a decrease of the mean size of the systems. Moreover, in agreement with what already observed in CMIP5 projections for the area, the models suggest an increase in the Central part of the Mediterranean region and a decrease in the South-eastern part of the region in the cyclone-related wind speed and precipitation rate. These rather two opposite tendencies observed in the precipitation should compensate and amplify, respectively, the effect of the overall reduction of the frequency of cyclones on the water budget over the Central and South-eastern part of the region. A pronounced inter-model spread among the RCSMs emerges for the projected changes in the cyclone adjusted deepening rate, seasonal cycle occurrence and associated precipitation and wind patterns over some areas of the basin such as Ionian Sea and Iberian Peninsula. The differences observed appear to be determined by the driving Global Circulation Model (GCM) and influenced by the RCSM physics and internal variability. These results point to the importance of (1) better characterizing the range of plausible futures by relying on ensembles of models that explore well the existing diversity of GCMs and RCSMs as well as the climate natural variability and (2) better understanding the driving mechanisms of the future evolution of Mediterranean cyclones properties.