This study aimed to investigate the seasonal variation of zooplankton diversity and abundance in the Nokoué Lagoon in southern Benin. Through extensive sampling, a total of 109 zooplanktonic taxa were identified and quantified. The average zooplankton abundance was found to be 60 individuals per liter, with copepods and rotifers being the most dominant groups, comprising 68.1% and 29.1% of the total abundance, respectively. The key factor identified as driving the structure of the zooplanktonic assemblages was salinity, which showed significant seasonal variation. The results revealed that during the high water period, when the lagoon was filled with fresh water, rotifers were dominant, zooplanktonic diversity was highest, and abundances were quite high. Conversely, during the low water period, when the lagoon was characterized by brackish water, diversity was minimal, and abundance decreased slightly. The study also found that some areas of the lagoon showed high abundances independent of salinity levels, suggesting that other factors such as riverine inputs or the presence of acadjas (home-made brush parks used as fish traps) may also have notable effects on the zooplankton community. Overall, the findings of this study provide valuable insights into the functioning of one of the most biologically productive lagoons in West Africa.