The combination of the filtration capacity of zooplankton (e.g. Daphnia) with the nutrient removal capacity of bacterial/algal biofilm in a zooplankton-containing reactor could provide a natural-based alternative for wastewater treatment. A laboratory-scale zooplankton-based reactor was tested at different HRTs resulting in a significant reduction in nutrient concentrations in wastewater when the system was operated at HRTs longer than 1.1 days (preferably of between 2 and 4 days). However, the presence of high concentrations of organic matter (>250 mg COD L−1) in the wastewater inhibited zooplankton activity, limiting its use to tertiary treatment. Therefore, in combination with other natural treatments that can perform primary and secondary treatments, zooplankton may provide a solution for wastewater clarification and nutrient polishing. The effect of a common metal such as copper on the filtration capacity of Daphnia was also evaluated. Daphnia, as well as the whole zooplankton-based reactor, adapted to copper concentrations of up to 70 μg Cu L−1 but an overload of 380 μg Cu L−1 for two-weeks severely affected the biological system.