Currently, climate change is a major concern around the world, especially because of the uncertainty associated with its possible consequences for society. Among them, fluvial alterations can be highlighted in basins whose flows depend on groundwater discharges and snowmelt. This is the case of the headwaters of the Tagus River basin, whose water resources, besides being essential for water uses within this basin, are susceptible to being transferred to the Segura River basin (both basins are in the Iberian Peninsula). This work studies the possible effects that the latest climate change scenarios may have on this transfer, one of the most important ones in southern Europe. In the first place, the possible alterations of the water cycle of the donor basin were estimated. To do this, a hydrological model was calibrated. Then, with this model, three climatic scenarios were simulated, one without climate change and two projections under climate change (Representative Concentration Pathways 4.5 (RCP 4.5) and 8.5 (RCP 8.5)). The results of these three hydrological modelling scenarios were used to determine the possible flows that could be transferred from the Tagus River basin to the Segura River basin, by simulating the water resource exploitation system of the Tagus headwaters. The calibrated hydrological model predicts, for the simulated climate change scenarios, important reductions in the snowfalls and snow covers, the recharge of aquifers, and the available water resources. So, the headwaters of the Tagus River basin would lose part of its natural capacity for regulation. These changes in the water cycle for the climate change scenarios used would imply a reduction of around 70%–79% in the possible flows that could be transferred to the Segura basin, with respect to a scenario without climate change. The loss of water resources for the Segura River basin would mean, if no alternative measures were taken, an economic loss of EUR380–425million per year, due principally to decreased agricultural production.