Petroleum contamination was assessed in indigenous and transplanted mussels for three types of environments within the Venice Lagoon and its associated interior canals. Indigenous and transplanted mussels were least impacted by petroleum contamination at open-water stations, but more affected in partially-enclosed areas indicating that physical processes of tidal or wind activities can remove organic contaminants such as petroleum from these areas more effectively. Limited tidal flushing of the interior canals resulted in contaminated locations unable to support indigenous mussels. Clean mussels transplanted to these highly impacted sites accumulated the highest levels of petroleum hydrocarbons. The distribution of polycyclic aromatic hydrocarbons (PAHs) indicated mainly combustion-related activities from sources such as the nearby industrial zones and boat traffic, with some evidence of fresher petroleum inputs. Total hydrocarbons found in all mussels could be related to concentrations found in the surrounding sediments as reported in an earlier study.