Karst springs are the exclusive source of water during dry months for many Mediterranean regions. The impact of climate change on the hydrology of Mediterranean karst springs has not received proper attention in the scientific literature. Specifically, the effect of climate change on the drought characteristics of karst springs has not been studied. Here, the response to climate change of three Mediterranean karst springs with different retention times is examined, focusing on the frequency, duration and intensity of their drought events. The Karst-SWAT model is used to quantify the karst springs flow. A set of representative climate change scenarios are used to assess the climate change impact on the springs and surface flow for the period 2019–2098. A non-parametric drought index is modified to estimate the future meteorological and hydrological drought characteristics in comparison to the reference period. The most adverse effects of climate change on the three karst springs are expected to prevail after 2059. Depending on the spring, the mean annual karst flow decreases from 14.2% to 25.1%, the mean number of drought events ranges from a decrease of 8.1% to an increase of 77.5%, the duration of drought events increases from 36.8% to 533%, and the mean monthly water deficit increases from 27.3% to 83.6%, when comparing the period 2059–2098 to the reference period (1979–2018). As the water retention time of the spring increases, the duration and intensity of the droughts are likely to increase more significantly. After 2059, multi-year droughts are forecast for all springs under all scenarios. Both low and high flows will increase, with the former occupying even wet months. The results of this study can be used as a guide for local and regional authorities and water management organizations, to adapt their practices for the mitigation of the impact of climate change on the water resources of Mediterranean karst springs.