Shallow-water, lithophilic spawning fishes are among the most vulnerable to anthropogenic fluctuations in water levels. We monitored water levels and environmental conditions at the nest sites of Moxostoma robustum (Robust Red-horse) on a main-channel gravel bar in the Savannah River, GA–SC. During the course of the 2005 spawning season, over 50% of the observed nest sites were either completely dewatered or left in near zero-flow conditions for several days. This occurred on two separate occasions, once early during the spawning season and then again near its conclusion. We hypothesize the habitat preferences of spawning Robust Redhorse leave them vulnerable to water-level fluctuations, and this phenomenon may be widespread in regulated river systems.