Intertidal organisms have to face daily high oxygen variations from hypoxic to hyperoxic conditions. To cope with such constraints, these organisms must have well developed compensatory mechanisms involving antioxidant and energetic adjustments. The oyster Crassostrea gigas is regularly exposed to high oxygen fluctuations and is a good model to understand these physiological regulations. This study aimed to explore the mechanisms involved in response to short-term oxygen variations in the digestive gland and hemocytes of C. gigas. The effects of returning into water after an emersion period were tested for 24 h at two different oxygen concentrations (normoxic 8.8 mg O2 L−1 and hypoxic 2.6 mg O2 L−1). Gene expression on several antioxidant enzymes was performed. In addition, a marker of oxidative damage, the malondialdehyde (MDA) was quantified. Hemocyte parameters measured were viability, concentration of different cellular sub-populations and oxidative activity. Changes in energetic metabolism were investigated measuring mRNA levels of pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK). Moreover, mRNA levels of the transcription factor HIFα were analyzed. Higher levels of the alternative oxidase (AOX) mRNA in normoxic conditions corroborate the hypothesis of the AOX having a role in the redox balance. MDA levels did not show any condition effect, suggesting that hypoxic conditions did not cause oxidative stress. mRNA levels of antioxidant enzymes and hemocyte oxidative activity increased during the 24 h of immersion. This suggests that the disruption of tidal cycles by maintaining oysters immersed resulted in an increase of oxygen-dependent activities. No clear hypoxic responses were detected neither in a switch of PEPCK and PK toward anaerobic metabolism, nor in HIFα regulation. PK mRNA levels were significantly higher in nomoxic conditions, suggesting that more elevated oxygen concentrations would lead to higher energetic metabolism. Hemocyte concentrations were higher in hypoxic conditions suggesting an increased hematopoiesis. This study brings new insights in understanding how oysters, and more in general intertidal molluscs, cope with short-term oxygen variations.