We investigated the hemolymph oxygen and acid–base status of Akoya pearl oysters, Pinctada fucata martensii, exposed to hypoxic seawater to elucidate the acid–base balance. Akoya pearl oysters cannulated to the anterior aorta for hemolymph collection from the submerged animals showed oxygen and acid–base disturbance of the hemolymph during environmental hypoxia for 24 h (O_2 partial pressure in seawater, Pwo_2 8 torr). The hemolymph O_2 partial pressure (Po_2) decreased from 72.2 torr to 13.6 torr, pH decreased from 7.581 to 7.129, and CO_2 partial pressure (Pco_2) increased from 0.86 torr to 3.31 torr during hypoxia. The hemolymph total CO_2 concentration (Tco_2) and bicarbonate ion concentration ([HCO_3^–]) were 1.93–1.95 mM/L and 1.80–1.91 mM/L, respectively, and there was no statistically significant change between pre-hypoxia and hypoxia for 24 h. When normoxic seawater was resumed after the hypoxia, the hemolymph Po_2, pH, and Pco_2 returned to their initial levels for about 3 h, and hemolymph Tco_2 and [HCO_3^–] gradually increased. These results showed that Akoya pearl oysters undergo hypoxemia and respiratory acidosis in the hypoxic environments for 24 h (Pwo_2 8 torr). In post-hypoxia, most of the disturbances disappeared within 3–24 h, and the increase in hemolymph [HCO_3^–] which was a secondary change compensated for respiratory disturbance.