AbstractClimate change will require species to adapt to new conditions or follow preferred climates to higher latitudes or elevations, but many dispersal‐limited freshwater species may be unable to move due to barriers imposed by watershed boundaries. In addition, invasive nonnative species may expand into new regions under future climate conditions and contribute to the decline of native species. We evaluated future distributions for the threatened European crayfish fauna in response to climate change, watershed boundaries, and the spread of invasive crayfishes, which transmit the crayfish plague, a lethal disease for native European crayfishes. We used climate projections from general circulation models and statistical models based on Mahalanobis distance to predict climate‐suitable regions for native and invasive crayfishes in the middle and at the end of the 21st century. We identified these suitable regions as accessible or inaccessible on the basis of major watershed boundaries and present occurrences and evaluated potential future overlap with 3 invasive North American crayfishes. Climate‐suitable areas decreased for native crayfishes by 19% to 72%, and the majority of future suitable areas for most of these species were inaccessible relative to native and current distributions. Overlap with invasive crayfish plague‐transmitting species was predicted to increase. Some native crayfish species (e.g., noble crayfish [Astacus astacus]) had no future refugia that were unsuitable for the modeled nonnative species. Our results emphasize the importance of preventing additional introductions and spread of invasive crayfishes in Europe to minimize interactions between the multiple stressors of climate change and invasive species, while suggesting candidate regions for the debatable management option of assisted colonization.Efectos del Cambio Climático, Especies Invasoras y Enfermedades sobre la Distribución de Cangrejos de Río Europeos Nativos