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Climate change is threatening natural ecosystems in the Earth, and arid regions of southern Africa are particularly exposed to further drying. Welwitschia mirabilis Hook. (Welwitschiaceae) is an unusual gymnosperm tree that is recognized as an icon of the Namib Desert, southern Africa. Many aspects of its biology were investigated in the past, with a special emphasis for its physiology and adaptations, but nothing is known about its potential sensitivity to current climate changes. In this study, we adopted an approach based on distribution data for W. mirabilis and ecological niche models for clarifying the species-climate interactions and for predicting the potential impacts of climate change on W. mirabilis populations in three well-separated sub-ranges (northern, southern and central) in northwestern Namibia, southern Africa. We evidenced that the populations occurring in the northern sub-range have peculiar climatic exigencies compared with those in the central and southern sub-ranges and are particularly exposed to the impact of climate change, which will consist of a substantial increase in temperature across the region. These impacts could be represented by demographic changes that should be detected and monitored detailedly to plan efficient measures for managing populations of this important species on the long-term scale.