The release of treated municipal wastewaters to the aquatic environment raises concern about the health impacts on local resident invertebrates such as mussels. The purpose of this study was to examine the immunotoxicity of two types of treated municipal effluents—physico-chemical treated and physico-chemical with additional ozonation—to freshwater mussels. Immunocompetence was followed by tracking changes in hemocyte viability, adherence, phagocytosis, vitellogenin (Vtg)-like proteins and the pro-inflammatory precursors nitric oxide (NOx) production and arachidonate cyclo-oxygenase (COX) activity. The study results revealed that following a two-week continuous-flow exposure to the effluents, a reduction in hemocyte viability, adherence, NOx and COX activities was observed. Vtg like proteins were also increased, highlighting the estrogenic nature of the effluents. A significant correlation was found between Vtg-like proteins and the phagocytic efficiency index (r=0.34; p<0.001), which suggests that estrogenic compounds may have been involved in the immunocompetence of mussels exposed to municipal effluents. In conclusion, short-term exposures to treated municipal effluents have the potential to impede the immunocompetence of mussels occurring in the vicinity of an effluent dispersion plume.