Thermo-mineral springs are specific ecosystems with extreme physicochemical conditions. Scattered throughout the landscape, these springs offer interesting models to study meta-community processes for small organisms living in these particular habitats. In this study, we used benthic diatoms communities to assess the importance of habitat size, habitat isolation, spatial configuration, physico-chemical and climatic conditions in structuring their assemblages. We sampled 54 thermo-mineral springs located in the Massif Central in France, where we measured 42 morphological, chemical and climatic parameters. We tested the species-area relationship for all springs and for several group of springs classified according to their environmental and hydrochemical composition. We also tested the distance-decay hypothesis and examined the relationships between environmental variables and local diversity (species richness, Shannon and Piélou indices). We finally evaluated the relative importance of spring morphology, water chemistry, climate and space on species composition. We failed to find any significant species-area or as well as any significant distance decay relationships, suggesting that ecological processes related to regional effects are of minor importance for benthic communities of thermo-mineral springs. However, environmental variables strongly explained species diversity and composition, emphasizing the well-known dependence of benthic diatoms to local environmental conditions. Yet, we found that some spatial structure may explain part of the species composition and still needs to be further investigate. Finally, this study provides new insights into the functioning of diatoms communities in thermo-mineral springs and should contribute to the conservation of these ecosystems at the regional scale.