As exotic species are introduced and spread across a heterogeneous landscape, the abundance and richness of potential competitor and prey species they encounter will vary. Little is known about the interactions between Bythotrephes longimanus and native predatory macroinvertebrates (e.g., Mysis, Chaoborus), which potentially limit the establishment and spread of the invader. An 80-lake survey was conducted in the summer of 2007 to obtain macroinvertebrate abundances across invaded and non-invaded lakes. A subset (15) of these lakes was surveyed more intensively to obtain stratified daytime and night-time distributions of the organisms. Overall co-occurrence of Bythotrephes with native macroinvertebrate predators was widespread across lakes indicating that the presence of native macroinvertebrates alone is unlikely to limit the establishment of Bythotrephes. However, we did find an effect of native macroinvertebrate predators on the vertical distribution of Bythotrephes: as native macroinvertebrate abundances increased, the relative abundance of Bythotrephes in the epilimnion increased. Furthermore, the relative abundance of some zooplankton prey (e.g., Daphnia) was lower in the epilimnion when Bythotrephes abundance was high. Although we cannot rule out consumptive effects, some evidence suggests an avoidance behavioural response in the prey. While the underlying mechanisms of these distributional shifts remain unclear, our results suggest that interactions between Bythotrephes, native macroinvertebrates and zooplankton prey are complex, highlighting the need to further examine these interactions.