Mimachlamys varia is a sub-littoral bivalve encountered from Norway to the Mediterranean Sea, which lives mostly byssally attached to rocks. During the low tide period, M. varia individuals, located highest on the shore, may experience short time of aerial exposure and face a low availability of oxygen. Here we report a comparative metabolomic profiling of gill samples of M. varia obtained by both LC-QToF and APGC-QToF mass spectrometry, to analyze metabolic changes occurring during emersion in comparison with immersion. Scallops were grown in aquaria with a simulated intertidal environment mimicking short-duration air exposure that they might experience during extreme tides: alternating 2 h emersion and 10 h immersion. Our results show a switch from aerobic to anaerobic metabolism after only 2 h of emersion, with the resort to different pathways: glucose-lactate, glucose-succinate and aspartate-succinate pathways. Furthermore, carnitine-conjugated metabolites were found to accumulate during emersion, as well as urate. The level of tyrosine on the contrary was found to decrease. These findings indicate a complex metabolic reprogramming that occurs after a two hour emersion period and upon re-immersion. Furthermore, M. varia is used as sentinel species in pollution biomonitoring, through the assay of biomarkers to evaluate the effects of pollutants. Here we show that emersion induces a significant decrease of superoxide dismutase activity, an enzyme developed by bivalves to face oxidative stress and used as biomarker. These findings have to be taken into account to normalize sampling during campaigns of environmental monitoring, by taking in situ, as far as possible only immersed individuals.