Climate change may impair the survival of rare species. In this study we used populations of the critically endangered pearl mussel Margaritifera margaritifera (Linnaeus, 1758) colonizing several rivers in the North of Portugal (the southern limit of their distribution) to assess the effects of future climatic scenarios. Our results, based on empirical and modelling data, showed that future survival is threatened by projected declines in precipitation for the 21st century, with implication on the river flows and water depths that might decrease below the species requirements. This situation could be especially critical during summer conditions since the ecological flows may not be assured and several river stretches may be converted into stagnant isolated pools. Connectivity may also be affected with reverberating effects on the mobility of Salmo trutta, the natural host of M. margaritifera, with consequences in the reproduction and recruitment of pearl mussels. In addition, the occurrence of extreme events such as droughts may also negatively affect pearl mussels. During the extreme 2017 summer drought we assessed the mortality of M. margaritifera in several Portuguese rivers. We found that massive die-offs occurred due to the low water level and mussels were mainly found stranded near the banks. Additionally, in some sites predation by wild boars (Sus scrofa (Linnaeus, 1758)) was also important. In view of future climatic scenarios, several M. margaritifera populations in Iberia (and elsewhere) may now be more at risk and conservation measures should be urgently applied, including: the negotiation of ecological flows with dam promoters, the restoration of riparian vegetation along degraded areas, supplemental stocking of hatchery-raised M. margaritifera individuals, and careful monitoring and translocations to deeper areas or ex-situ facilities to reduce mortality rates during summer extreme droughts.