Sediment quality was assessed at multiple sites in the lower Oconee River, GA to identify contaminants potentially affecting the survival of an endemic “At-Risk” species of fish, the robust redhorse (Moxostoma robustum). Five major tributaries that drain urban and agricultural watersheds enter this stretch of river and several carry permitted municipal and industrial effluents containing Cd, Cu, and Zn. Sediments for chemical analyses and toxicity tests with Hyalella azteca (Amphipoda) were collected at 12 locations that included sites above and below the major tributaries. Compared to national data bases and to the nearby Apalachicola-Chattahoochee-Flint watershed, sediments from the Oconee River had elevated concentrations of Cr, Cu, Hg and Zn. Zinc concentrations showed a marked increase in sediment downstream of the confluence of Buffalo Creek demonstrating contributions from permitted municipal and industrial effluents discharged to that tributary. When exposed to these sediments, growth of H. azteca was significantly reduced. Amphipod growth was also reduced when exposed to sediments collected from another site due to toxicity from Cr. Sediments in the lower Oconee River appear to be impaired due to metal contamination and could pose a threat to organisms, such as the robust redhorse, that are closely associated with this matrix during their life cycle.