The central Platte River is an important resource in Nebraska. Its water flows among multiple channels and supports numerous beneficial uses such as drinking water, irrigation for agriculture, groundwater recharge, and recreational activities. The central Platte River valley is an important stopover for migratory waterfowl and cranes, such as the Whooping (Grus americana) and Sandhill Cranes (Grus canadensis), in their annual northward traversal of the Central Flyway. Waterfowl, cranes, and other migratory birds moving across international and intercontinental borders may provide long-range transportation for any microbial pathogen they harbor, particularly through the spread of feces. Samples were collected weekly in the study reach from three sites (upstream, middle, and downstream from the roosting locations) during the spring of 2009 and 2010. The samples were analyzed for avian influenza, Escherichia coli, Cryptosporidium, Giardia, Campylobacter, and Legionella. Analysis indicates that several types of fecal indicator bacteria and a range of viral, protozoan, and bacterial pathogens were present in Sandhill Crane excreta. These bacteria and pathogens were present at a significantly higher frequency and densities in water and sediments when the Sandhill Cranes were present, particularly during evening roosts within the Platte River environment.