Mercury (Hg) contamination is believed to be one of the most significant pollution hazards to wildlife in the southeastern United States, yet comprehensive studies of Hg contamination of piscivorous raptors are rare in this region. We analyzed total Hg (THg) concentration in tissues of 39 osprey (Pandion haliaetus) primarily from coastal counties of South Carolina, USA, to describe tissue distribution of Hg and to determine whether age or sex influenced Hg accumulation. To determine whether Hg poses health risks to osprey breeding in this region, we also measured selenium in all tissues and the percentage of THg that was methylated in a subset of individuals. Osprey with adult plumage tended to have higher and more variable Hg concentrations in their tissues than younger birds. Whereas highest concentrations of Hg were found in liver and kidney of older birds, chicks had highest concentrations in keratinized tissues. Mercury concentrations were correlated between feathers and soft tissues, but talon concentrations of Hg were better correlated with organs than to feathers in most cases. Contrary to previous studies on birds, we found no relationship between Hg concentration in primary feathers and the sequence in which the feather was molted. We attribute this observation to the irregular and protracted molting pattern of osprey. Also contrary to other studies, feather concentrations of Hg were considerably lower than concentrations in liver and kidney. Osprey with high concentrations of Hg in their livers and kidneys accumulated as much as 99% of it as Hg(II), suggesting that demethylation and sequestration of Hg(II) may be even more critical to mitigating adverse effects than it is for other birds that eliminate most of their Hg burden in feathers. In addition, selenium was co-sequestered with Hg in the liver and kidneys and may further mitigate any adverse effects. Based on these findings, we suggest that most osprey in this region are not currently at risk of Hg toxicosis, but recommend that additional ecotoxicological studies be performed to monitor risk to osprey in this coastal region facing heavy development. We also suggest that concentrations of Hg in talon and claw may serve as important indicators of previous exposure and provide useful information for natural resource managers seeking to assess health risks to birds.