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The availability of freshwater to meet human and natural ecosystem needs remains the ultimate challenge of ecologically sustainable water management. This issue is particularly true in the southwestern United States, such as Texas, where water resources are already over allocated. The San Saba River, located in central Texas, exemplifies this issue as excessive water withdrawal has resulted in intermittency for as much as two-thirds of its length. The effect of this dewatering on aquatic species such as mussels is not well known, which is problematic because five species of high conservation concern occur in this river. The goal of this study was to examine how dewatering may have affected the distribution of these species and to identify options for mitigating this threat. Comparing species-per-unit-effort (SPUE) and catch-per-unit-effort (CPUE) between these reaches, we found SPUE and CPUE were 3.7 and 7.9 times lower, respectively, in intermittent reaches than in perennial reaches. Using fuzzy ordination, we found that mussel assemblage structure differed between intermittent and perennial reaches despite both historically sharing similar fauna. Evaluating habitat, we found differences in mussel-mesohabitat associations between perennial and intermittent reaches. Current water policy and regulatory tools to mitigate this issue are insufficient, which raises serious questions about how states like Texas, located in arid and semi-arid regions, will be able to protect aquatic ecosystems under the specter of ever increasing population growth and climate change. Keywords: Human impacts, Dewatering, Southwestern United States, Biodiversity, Imperiled species, Unionid mussels