Following the collection of a putative undescribed species in the genus Pleurobema in 2012, we surveyed the freshwater mussel fauna of Little River, Blount County, TN, to determine species diversity and relative abundances. At 18 main-stem sites, we sampled 3053 live specimens representing 12 mussel species and 1 fresh-dead individual representing another. An additional species represented by a relic shell was collected, bringing the total to 14 mussel species sampled during this survey. Villosa species comprised 77% of total live mussels sampled. Among the extant mussels were two federally endangered species: Fusconaia cuneolus (Finerayed Pigtoe) was confirmed to persist in the river, while Pleuronaia dolabelloides (Slabside Pearlymussel) represents a new drainage record. Several other mussels collected are considered imperiled globally, including Alasmidonta viridis (Slippershell Mussel), Lampsilis ovata (Pocketbook), Medionidus conradicus (Cumberland Moccasinshell), Pleurobema oviforme (Tennessee Clubshell), Pleuronaia barnesiana (Tennessee Pigtoe), and Villosa vanuxemensis (Mountain Creekshell). A total of 319 individuals of the putative new species Pleurobema sp. cf. oviforme were sampled at 9 sites, 215 at 1 site. A total of 857 individuals of a putative undescribed species in the genus Villosa were sampled at 9 sites. These 2 putative species (Pleurobema sp. cf. oviforme and Villosa sp. cf. iris) are likely endemic to Little River, TN, and may be in need of state and federal protection. Mussel densities declined downstream from the mouth of Ellejoy Creek, indicating that water-quality issues may be occurring in this reach of the river.