Spatial and temporal variation in planktons and water quality parameters were investigated in order to determine the effects of seasonal water use on reservoir water quality and planktons' diversity in Kulekhani Multipurpose Reservoir, Nepal. This study also focuses on interactions among various water quality parameters with planktons and how such interactions can affect the second major utility, the fish farming in the reservoir. The analyses of seasonal water samples collected from three different sampling locations in the reservoir showed that select water quality parameters varied significantly (P < 0.05) with sampling seasons (transparency: 30 -250 cm, pH: 7 -7.5, alkalinity: 30 -120 mg/L, DO: 6 -11.5 mg/L, CO 2 : 0.1 -1.1 mg/L) and sampling locations (phosphate: 0.1 -0.25 mg/L, nitrate 0.01 -0.19 mg/L) in the reservoir. Three groups of zooplankton and four classes of phytoplankton, respectively with eleven and twelve genera, were identified and quantified in the reservoir.Among them, Cyclops, Asplanchana, and Keratella were most dominant zooplanktons while Synedra, Melosira and Peridinum were the most dominant phytoplankton in the reservoir water. The abundance of select zooplanktons (Cyclops, Keratella, Polyanthra), and phytoplankton (Navicula, Melosira, Amphora, Chroococcus, Staurastrum, Scendesmus) showed significant interaction between sampling sites and sampling seasons, while the other varied only with sampling seasons and/or sites. These results showed that seasonal water level fluctuations, along with the variation of water quality para- meters, change the abundance and diversity of planktons' in the reservoir. Such changes can negatively impact the fish in cage culture, affecting the livelihood of people extensively relying on these fish farming.