The Adriatic Sea is an enclosed basin threatened by marine pollution due to its hydrographic features and anthropogenic pressure. Although zooplankton has been worldwide regarded as an immediate warning signal of contamination, limited information is available on the contamination of these organisms at the Adriatic level. Hence, this study provides comprehensive data on the presence and levels of multiple pollutants in zooplankton collected from 46 locations. With regards to legacy contaminants, both PCB and DDT levels have declined since the 1980s. Specifically, most samples were characterized by low DDT contamination (average of 3 ± 2.7 ng g− 1 dry weight) and only few of these accumulated levels of concern for what concerns PCB, pointing out possible hotspots of contamination in the central-eastern Adriatic Sea. As regards metal(loid)s, the Metal Pollution Index identified areas of concern in the north Adriatic Sea (Gulf of Venice) with high levels of Co, Cu, Hg, Cr and Pb; in the Central Adriatic Sea (Tremiti islands) with high levels of Co, Ni, Hg, Cr and Pb; in the Southern Adriatic Sea (Taranto and offshore Corfu), with high levels of most metal(loid)s, especially Cr, Ni and Zn. Certain metal(loid)s (e.g. Cd, Pb and Hg) have declined over time and most of them are lower than well-known contaminated worldwide marine ecosystems. Only Cu appears to be particularly high in the Mediterranean zooplankton. Overall, this work suggests a general improvement of the status of contamination of the Adriatic Sea.