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Transformation, dissolution, and sorption of copper oxide nanoparticles (CuO-NP) play an important role in freshwater ecosystems. We present the first mesocosm experiment on the fate of CuO-NP and the dynamics of the zooplankton community over a period of 12 months. Increasingly low (0.08−0.28 mg Cu L −1 ) and high (0.99−2.99 mg Cu L −1 ) concentrations of CuO-NP and CuSO 4 (0.10− 0.34 mg Cu L −1 ) were tested in a multiple dosing scenario. At the high applied concentration (CuO-NP_H) CuO-NP aggregated and sank onto the sediment layer, where we recovered 63% of Cu applied. For the low concentration (CuO-NP_L) only 41% of applied copper could be recovered in the sediment. In the water column, the percentage of initially applied Cu recovered was on average 3-fold higher for CuO-NP_L than for CuO-NP_H. Zooplankton abundance was substantially compromised in the treatments CuSO 4 (p < 0.001) and CuO-NP_L (p < 0.001). Community analysis indicated that Cladocera were most affected (b k = −0.49), followed by Nematocera (b k = −0.32). The abundance of Cladocera over time and of Dixidae in summer was significantly reduced in the treatment CuO-NP_L (p < 0.001; p < 0.05) compared to the Control. Our results indicate a higher potential for negative impacts on the freshwater community when lower concentrations of CuO-NP (<0.1 mg Cu L −1 ) enter the ecosystem.