ABSTRACT1. The Leon River drainage, located in the Brazos River basin, has not been extensively surveyed for freshwater mussels (Family Unionidae). This is problematic given that three state-threatened species, Quadrula houstonensis, Quadrula mitchelli, and Truncilla macrodon, have historically occurred in this drainage and two are now candidates for protection under the US Endangered Species Act.2. Mussels were sampled qualitatively at 44 sites in the summer and fall of 2011 to determine whether these species were still extant in the Leon River. The distributions and abundances of species at present considered common were also examined. Shell length data were assessed to determine the overall viability of the mussel fauna within the Leon River drainage.3. In total, 2081 live mussels were collected representing 12 species, including the federal candidate species Quadrula houstonensis, but Lampsilis hydiana, Quadrula mitchelli and Truncilla macrodon were not collected. Overall mussel abundance and species richness was low and community composition was highly fragmented with riverine species largely occurring in the middle portion of the Leon River. There was evidence that population recruitment is occurring, but only for a few species.4. River impoundment, inadequate instream flows, and agricultural practices are probable causes of the changes in mussel species composition. Further studies are needed to evaluate the impacts of reservoir releases on mussel persistence within this basin and in areas where droughts and low stream flow are commonplace. More information is needed on how agricultural practices affect mussel communities; the information that is currently available does little in the way of identifying factors that can be managed at site or reach scales. Studies that address these knowledge gaps will help resource managers to design more effective strategies to protect mussel populations within and outside this basin.