The composition, abundance and functional diversity of zooplankton from the main channel of the Middle Paraná River were studied. Monthly samples were collected in both ordinary drought periods (1977, 1978, 1981, 2007) and extraordinary drought ones (La Niña events 1971-1972, 1999 -2000. A constant pattern of zooplankton structure was recorded from 1971 to 1981 characterised by a strong rotifer dominance. Changes were observed in the last two periods, with the planktonic larvae of Limnoperna fortunei as a new component of zooplankton. The abundance of zooplankton showed a significant interannual variability and a decreasing trend over time with the maximum values almost 100 times lower from 1999 onwards, mainly resulting from a decline in rotifer density. Cladocerans and copepods occurred with very low abundance and were similar across years. Bosmina and Bosminopsis showed a decreasing trend through time. Evidence was found of intrazooplanktonic competition between rotifers and cladocerans. Zooplankton and phytoplankton abundance presented similar trends, but the edible algal fraction (< 20 µm) showed a negative relation with Bosminidae, suggesting cladoceran control. In the last period, zooplankton changes were not associated with physical parameters (except flow velocity), nutrients or phytoplankton. The absence of a constant pattern and the causes of the declining trend of zooplankton abundance over time could be related to biotic interactions and multiple-stressors throughout the study.