The purpose of this study is to examine the response of the oyster Crassostrea gigas to sulphide at different biological scales. A first experiment was designed to measure for 20 h the clearance (CR) and oxygen consumption (OC) rates of oysters exposed at different concentrations of sulphide (0, 3, 6, 12, 20, and 40 μM). The second experiment was carried out to evaluate the metabolic adaptations to chronic sulphide exposure for 10 days by measuring PK and PEPCK enzyme activities, succinate and alanine content, the adenylate energy charge (AEC), and the activity of the electron transport system (ETS) in whole oysters at above 20 μM. PK and PEPCK mRNAs and enzyme activities have been measured in adductor muscle. When exposed to sulphide above 20 μM, CR stopped, whereas oyster maintained their average OC rate between 1 and 2 mg O₂ h⁻¹ g⁻¹ dw. In the second experiment, sulphide exposure of oysters resulted in higher mortality, reduced the glycolytic flux by inhibiting the PK activity and decreased the ETS activity leading to a lower AEC. At day 10, a kind of recovery took place: the ETS activity and AEC of oysters exposed to sulphide increased to the level of the control oysters. In the adductor muscle, sulphide did not affect the transcriptional level of PK; PK was only regulated at enzyme level. Conversely, PEPCK was regulated only at transcriptional level. Nevertheless, muscle exhibited a wholly anaerobic metabolism by the significant increase of alanine and succinate contents followed by the significantly decrease of the ATP content during the 10 days of the experiment. This experiment showed that sulphide involved partially the whole oyster and wholly the adductor muscle in an anaerobic pathway of energy production; but oxygen was needed for the detoxification of the organism.