Potential lethal and sublethal effects of oil from the Deepwater Horizon spill to oysters (Crassostrea virginica) in Louisiana east of the Mississippi River were examined along a biophysical gradient of oil pollution, salinity, and disease. Approximately 6 mo after the capping of the Deepwater Horizon wellhead, no polycyclic aromatic hydrocarbons were detected in oysters from oil-exposed sites. Variations in oyster condition and reproductive state, and infection with the oyster parasite Perkinsus marinus are consistent with natural differences along the salinity gradient and not with impacts of polycyclic aromatic hydrocarbon contamination.