Coastal ecosystems are periodically exposed to short- and long-term hypoxia. Coastal organisms are thus exposed to these hypoxic conditions, though, many intertidal species are tolerant to this situation. The hypoxia tolerant species can endure hypoxia through metabolic rate depression. However, the effect of hypoxia and the following reoxygenation phase on the homeostasis of the intermediate metabolites are yet to be understood. In this study, we focused on the effects of 1 day and 6 days of hypoxia and 1 hour of reoxygenation after each hypoxic conditions on the homeostasis of the intermediate metabolites in the gill and helatopancreas tissue of two intertidal species, Mytilus edulis and Crassostrea gigas. According to our findings, the effect of hypoxia and reoxygenation on the intermediate metabolites in hypoxia tolerant C. gigas were (s)lower compared to the more sensitive M. edulis. The observed changes in multiple metabolic pathways were consistent with the higher resistance to oxidative injury during hypoxia-reoxygenation.