Establishment of non-native species can alter native species populations and restructure lake food webs through complex tropic interactions such as intraguild predation or classic trophic cascades. Although the freshwater shrimp Mysis diluviana is well known for its ability to impact both primary and secondary productivity through omnivorous feeding in aquatic ecosystems in which it has been introduced, empirical evidence of mysid consumption of zooplankton prey and associated impacts on cladoceran communities from the same lake is uncommon. Furthermore, recent literature has suggested that mysids may impact other zooplankton populations outside of cladocerans. To test the hypothesis that introduced mysids negatively affect the seasonal abundance of cladocerans in Lake Pend Oreille, a large and deep (348 km2, max. depth: 352 m) lake in Idaho, USA, we quantified the seasonal diet and consumption rates of mysids and compared them with cladoceran production rates. During isothermal conditions, mysids opportunistically fed on copepods, diatoms, and rotifers. However, during stratification, mysids strongly selected cladocerans. In addition, during isothermal conditions, mysids consumed 100% of cladoceran production and selected reproductive-sized individuals. We interpret this to show that mysids regulate the production of cladocerans when the lake is not stratified. The suppression of cladocerans in the spring coincides with the appearance of kokanee (Oncorhynchus nerka) fry whose growth and survival may be negatively affected by the lack of abundant cladocerans, a preferred prey. This suggests a possible cascading effect to higher trophic levels.