This study investigated the residues of 19 organochlorine pesticides, 37 antibiotics and 5 heavy metals in biota samples (one mussel species, one crayfish species, six wild fish species and one farmed fish species) from the Keban Dam Reservoir on the Euphrates River, Turkey. Among monitored OCPs, only p,p′-DDE was detected in biota samples. It was found only in mussel, fish muscle and fish gill samples. The highest concentration of p,p′-DDE (0.032 mg/kg ww) was determined in the gill of common carp, which was found to be below the maximum residue limit (MRL). Only sulfadimethoxine was detected among antibiotics in biota samples. Its maximum concentration (0.0044 mg/kg ww) did not exceed the MRL of 0.1 mg/kg. Sulfadimethoxine was found only in muscle and gill of common carp collected from site S6, where there are many rainbow trout cage farms. However, no detectable residue of sulfadimethoxine was found in farmed rainbow trout. The highest concentrations of As, Cd and Pb were detected in mussels, while the highest concentrations Cu and Zn were determined in crayfish. Metal concentrations in biota samples did not exceed the maximum permissible levels. According to these results, the consumption of biota samples from the Keban Dam Reservoir is safe for human health.