Dreissena (Bivalvia: Dreissenidae) species can act as ecosystem engineers, physically altering freshwater ecosystems and changing benthic macro-invertebrate assemblages. The mussel beds they form can provide shelter and food for detritivorous species, whereas fouling can directly impact native bivalves. In this study, we examined the effects of the zebra mussel (Dreissena polymorpha) and quagga mussel (Dreissena rostriformis) on the macro-invertebrate community in the Meuse River by characterizing the macro-invertebrate assemblage associated with Dreissena clumps on artificial substrates at four sampling sites and by quantifying the infestation of Dreissena on native mussels along six transects. We found that the study site with dense Dreissena clumps on artificial substrates hosted particular macro-invertebrate assemblages that were composed of amphipods, gastropods and some insect larvae. Oligochaeta and Ephemeroptera abundances were low at this site. Non-native Ponto-Caspian amphipods occurred in very high densities in mussel beds, and we report the first records of several new invasive amphipod species in the Meuse River. Our results also revealed that ca. 40 % of sampled Unionidae were infested by Dreissena, although infestation load was low (0.48–2.51 Dreissena per native bivalve). These results suggested that the interactions between Dreissena and other macro-invertebrates ranged between a probably low incapacitating relationship with Unio resulting from a long coexistence which allowed the two species to live in sympatry and a strong facilitation for exotic amphipods native from the same region as Dreissena.