In the semi-arid Andes Cordillera of central Chile (31–36°S), mountain glaciers are important reservoirs of freshwater, especially during droughts, contributing between 70 and 80% of the total runoff. In this work, we use the physically-oriented and spatially-distributed TOPKAPI-ETH glacio-hydrological model to simulate the response of glaciers to severe droughts in the Olivares River catchment. The glacierized area of this catchment is equivalent to 26% of the total glacier area in the Maipo River basin, the main source of surface water for Santiago de Chile – where more than 40% of the population in the country lives. To this end, we force TOPKAPI-ETH with synthetic droughts under several scenarios of glacier retreat, defined by two climate scenarios: i) current climate, preserving the mean and standard deviation of precipitation and temperature observed during the period 1990-2009, and ii) considering the Paris Agreement and constraining the global temperature rise – relative to preindustrial levels – to 1.5°C, projected by a small number of climate models under the RCP2.6 long-term scenario. We also use outputs from regional climate model simulations generated by the Center for Climate and Resilience Research (CR2) to represent what would be an increase of mean temperature in our domain. To assess the hydrological response of glaciers, and the contribution to total runoff under these scenarios, we compare our results with those obtained for droughts observed in this region during 1967-1969 and 2010-2015, considered as the most important events to date in Chile. Ongoing efforts are oriented to quantify ice loss under current climatic conditions, elevation line altitude variations during the long-term simulation, variations in glacier area and volume, and basin response to future drought under glacier retreat scenarios. Preliminary results show that glacier relative contribution to runoff at the end of the summer season increases up to 25% during the reference droughts, but decreases about 40% to 75% in comparison to the reference period considering climate scenarios.