Lake Iseo is a deep meromictic lake located in Italy. During the past 20 years (1993–2013), the lake has experienced complete mixing of the water column only in spring 2005 and 2006. The full overturn episodes in these 2 years resulted in an increase in nutrients in both years, but an increase in phytoplankton biovolume occurred in the surface layers only in 2005. Our study examined if the magnitude of vertical mixing and the resulting increase in concentrations of epilimnetic total phosphorous (TP) can help predict reproduction and abundance of the main primary consumers, the cladocerans. We investigated the lake for 9 years (2001–2009) and compared annual changes in the Cladocera community and reproduction of the Daphnia longispina group between years of full and partial mixing. During the complete vertical mixing years (2005 and 2006), the taxonomical composition of Cladocera did not change, and density relationships among taxa shifted slightly toward an increase in the population density of Daphnia spp. Phytoplankton biovolume was significantly related to Daphnia mean clutch size. The increase in TP subsequent to the complete vertical mixing during late winter–early spring also seemed to predict reproduction and population density of Daphnia species. To our knowledge, this is the first long-term field study highlighting the importance of vertical mixing depth and TP concentrations on Daphnia abundance and phenology in a meromictic–oligomictic deep lake.