Wild birds have been shown to be significant sources of numerous types of pathogens that are relevant to humans and agriculture. The presence of large numbers of migratory birds in such a sensitive and important ecosystem as the Platte River in central Nebraska, USA, could potentially serve a significant source of bird-derived pathogens in the water/sediment and riverine environment. In 2009 and 2010, a study was completed to investigate the potential water-quality impacts of Sandhill Cranes and Snow Geese on the microbial water quality of the central Platte River during their spring migration period. Fecal material, river-bottom sediment, and water samples were collected from January through May of each year during the spring migration season of Sandhill Cranes in the Central Flyway of North America. Results indicate that several types of fecal indicator bacteria and from a range of viral, protozoan, and bacterial pathogens, Campylobacter jejuni were present in Sandhill Crane excreta, and at significantly higher frequency and densities in water and sediments when the Sandhill Cranes were present, particularly during evening roosts within the Platte River environment. Therefore, further investigation of the health significance of avian pathogens is warranted for the Platte River in Central Nebraska during migration of Sandhill Cranes and other waterfowl.