Dreissena polymorpha is a sentinel freshwater mussel providing key functional ecosystemic services like nutrient recycling and suspended matter filtration. Global warming and especially extreme events imply rapid fluctuations of environmental parameters that sessile organisms could not escape. The increase occurrence of heat waves and the subsequent expansion of hypoxic areas could challenge the survival of mussels. This study provided a deeper knowledge of energy management and cellular function during thermal (+15 ◦C) or hypoxic (30% of dissolved oxygen saturation) stress for 7 days. A potential metabolic rate depression was highlighted in D. polymorpha under hypoxia through a decline in the mitochondrial activity and a constant AMP content over time. A contrasted pattern of response was observed in thermal-stressed mussels between 24 h and 7 days of exposure. A global increase of metabolic activity was noticed in mussels after 24 h while a return to control level was noticed at the end of the experiment. Although D. polymorpha is considered as a temperature tolerant species, a significant increase of ADP:ATP ratio, related to a decrease of mitochondrial activity and density, suggested an overwhelming of organisms. This study pointed to the importance of considering time of exposure to natural factor variations in tolerance window of organisms in a long-term changing environment. The apparent short-term tolerance of D. polymorpha could hide much more deleterious consequences, i.e. mortality, if abiotic stresses persist, as suggested by climate change models.