Intertidal species face multiple stressors on a daily basis due to their particular habitat. The submergence at high tide in the aquatic environment and emergence at low tide to the aerial environment, associated with a wide variation of abiotic parameters, along with anthropogenic contamination are some of the daily stresses that these organisms are exposed to. With such a dynamic environment, organisms developed strategies that allow them to avoid or tolerate these stressors. Among these species, bivalves are some of the most hypoxia tolerant, being commonly used as a biomonitoring tool due to their capacity to accumulate pollutants from the environment and reflect the imposed toxic impacts. However, when evaluating the response ability of organisms to different stressors under laboratory conditions, it is not common to consider the fact that exposure to tides can act as a confounding factor. The present study assessed the effects of air exposure on the biochemical (metabolic capacity, energy reserves, and oxidative stress related biomarkers) performance of intertidal Mytilus galloprovincialis mussels. Specimens of M. galloprovincialis were submitted once every 24 h to different periods of air exposure (3 and 6 h) for 14 days, under constant air and seawater temperature (19 ± 1 °C). Results obtained revealed that air exposure can cause biochemical changes in mussels. The present findings demonstrated that individuals exposed to air induced superoxide dismutase (SOD) and catalase (CAT) activity as mechanisms to withstand the abiotic changes while mobilizing lipid content as the principal source of energy, and increasing protein content possibly as a result of an increase in the number of antioxidant defense enzymes. Moreover, individuals under air exposure suffered higher oxidative damage while showing higher metabolic rate. Results demonstrated that longer periods of air exposure induced more injuries, since individuals emerged during 6 h presented higher oxidative stress than individuals under 3 h of air exposure.