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Climate models project a reduction in annual precipitation and an increase in temperature, which may lead to runoff shortages and a consequent water availability reduction, in some Mediterranean regions, such as southern Portugal. The impacts on water availability under different climate change scenarios are assessed using SHETRAN, a physically-based and spatially-distributed hydrological model. SHETRAN is calibrated and validated against daily runoff measurements at outlet and internal sections and against phreatic surfaces using a multi-basin, multi-location and multi-response approach. Nash-Sutcliff efficiency, volume deviation and coefficient of determination ranged, respectively, from 0.58 to 0.76, 0.59 to 0.79 and −9 to 15 %, in the calibration period, and from 0.54 to 0.75, 0.54 to 0.77 and −14 to 12 %, in the validation period. Three GCM and two RCM are used for control (1961–1990) and scenario (2071–2100) periods, under the A2 SRES emission scenario. Observed bias in the climate models’ projected precipitation and temperature are corrected with three bias correction methods. For the scenario period the climate models project a change in precipitation from +1.5 to −65 % and an increase in temperature from +2.7 to +5.9 °C. This trend in climate change projection is reflected in the annual runoff that decreases drastically, between 13 and 90 %, in southern Portugal by the end of the century. The runoff reduction is greater in all watersheds in Autumn and Spring with higher agreement between models and bias correction methods. The runoff decrease seems greater in the Guadiana river basin which is already under significant water stress. © 2015, Springer Science+Business Media Dordrecht.