Invasive zebra (Dreissena polymorpha) and quagga (Dreissena rostriformis bugensis) mussels are Ponto-Caspian species that settled in the Moselle River since a long time for the first (19th century) and more recently for the second (in the 2000s). The dredging monitoring of macroinvertebrate communities in four stations provides data about abundances of the two species and the decline of zebra mussels’ populations was recorded. The settlement of the quagga mussel leads to a dynamic equilibrium where the two species seem to coexist by presenting different strategies. Reproduction is a key biological process and our results show that quagga mussels have a wider period of potential dispersion with gamete emission beginning in summer and lasting until winter. The monitoring in both species of parameters relative to the energy metabolism (energetic reserve, enzymes of anaerobic and aerobic pathways to provide cellular ATP) suggests that quagga mussels invest more their energy in reproduction than in tolerance to stress, whereas the zebra mussels present an opposite strategy. We compared the tolerance of several populations of both species through a laboratory test where we exposed individuals to a high concentration of Nickel (2.5 mg/L) in order to discriminate the populations/species upon their ability to survive. The calculation of the lethal time 50% conducted us to observe that the zebra mussels’ populations were more tolerant than quagga mussels’ ones. The tolerance was associated to higher levels of cellular defense (enzymes involved in anti-toxic mechanisms) in zebra than in quagga mussels. In the global change context, where we are not able to understand finely and even less able to control future trajectories, we think that studying ecophysiological reactions of invasive species is a relevant way to describe and understand the potential impacts on ecosystems of accelerated changes (warming, pollution, other invasions).