A screening ecological risk assessment (ERA) was conducted for the first time in the Mediterranean basin in order to assess the toxicity posed to the benthic community by PCBs, DDTs and HCB in marine sediments. The characterization of the exposure was conducted by means of an extensive literature survey, generating a database with more than 2000 samples. The effects were assessed by the adoption of guidelines previously developed in the literature, because ecotoxicological information about persistent organic pollutants (POPs) in the Mediterranean sediments was lacking. Existing sediment quality guidelines (SQGs) for the target pollutants were compiled and consensus values were calculated for three different categories of toxicity, namely threshold effect concentration (TEC), probable effect concentration (PEC) and extreme effect concentration (EEC). The combination of exposure and effects characterization enabled the identification of some areas of concern in the vicinity of industrial and urban locations and in the mouths of the main Mediterranean rivers. Beyond the Mediterranean continental shelf, the level of toxicity for the benthic community was generally low. The evaluation of the toxicity induced by the mixture of the target pollutants spotted the importance of DDT contamination in the Mediterranean sediments, despite the fact that main inputs to the sea have been significantly reduced during the last decades.