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Perfluorinated chemicals (PFCs) are of concern due to their widespread use, persistence in the environment, tendency to accumulate in animal tissues, and growing evidence of toxicity. Between 2006 and 2011 we collected blood plasma from 261 bald eagle nestlings in six study areas from the upper Midwestern United States. Samples were assessed for levels of 16 different PFCs. We used regression analysis in a Bayesian framework to evaluate spatial and temporal trends for these analytes. We found levels as high as 7370 ng/mL for the sum of all 16 PFCs (Sigma PFCs). Perfluorooctanesulfonate (PFOS) and perfluorodecanesulfonate (PFDS) were the most abundant analytes, making up 67% and 23% of the PFC burden, respectively. Levels of Sigma PFC, PFOS, and PFDS were highest in more urban and industrial areas, moderate on Lake Superior, and low on the remote upper St. Croix River watershed. We found evidence of declines in Sigma PFCs and seven analytes, including PFOS, PFDS, and perfluorooctanoic acid (PFOA); no trend in two analytes; and increases in two analytes. We argue that PFDS, a long-chained PFC with potential for high bioaccumulation and toxicity, should be considered for future animal and human studies.