Whereas the data on mesozooplankton in the epipelagic offshore Mediterranean Sea are extensive, less information is available about plankton in the deeper layers. The present study aims to describe the vertical and horizontal structure and distribution of mesozooplankton species and their associations down to 1,200 m in the water of the Southern Adriatic Sea. Zooplankton were sampled using a Nansen net of 200‐μm mesh size during two cruises in the winters of 2015 and 2016, extending from the coast to the open sea. In total, 203 zooplankton taxa were identified. The community was dominated by copepods, representing between 67% and 91% of the total abundance. The highest total densities were recorded in the upper layers where a high proportion (up to 36%) of appendicularians was also observed in the first sampled year. Five groups of samples were determined based on their community structure. In 2015 communities were distinct between the 0 and 50 m layer and the underlying one (50–100 m), whereas in 2016 epipelagic waters were inhabited by a more uniform mesozooplankton community. The mesopelagic and deep‐water fauna, especially copepods, showed a relatively stable composition in both sampling years Overall, our study confirms the oligotrophic character of the Southern Adriatic, with occasional density outbreaks of appendicularians under favourable conditions.