Dreissenid mussels have been hypothesized to cause selective decreases of phytoplankton innearshore areas (nearshore shunt hypothesis) as well as the near-complete loss of the offshore phytoplankton spring bloom in some Laurentian Great Lakes. To evaluate whether mussels can reasonably be expected to mediate such changes, we extended the threedimensional hydrodynamic-ecological model (ELCOM-CAEDYM) to include mussels as a state variable and applied it to Lake Erie (USA-Canada). Mussel-mediated decreases in mean phytoplankton biomass were highly sensitive to the assigned mussel population size in each basin. In the relatively deep east basin, mussels were predicted to decrease phytoplankton in both nearshore and offshore zones, even during periods of thermal stratification but especially during the spring phytoplankton maximum. Spatially, impacts were associated with mussel distributions but could be strong even in areas without high mussel biomass, consistent with advection from areas of higher mussel biomass. The results supported the nearshore shunt hypothesis that mussel impacts on phytoplankton should be greater in nearshore than offshore waters and also supported suggestions about the emerging importance of deep water offshore mussels. The results of this study provide an important insight into ecological role of mussels in lowering plankton productivity in some world’s largest lakes.