This work concerns the effects of cadmium exposure on the anaerobic and oxidative metabolism in tissues of the hypoxia-tolerant green mussel Perna viridis from Venezuelan coastal waters. The mussels were exposed to different Cd concentrations (0, 20, 40 and 60 µg/L Cd) for 7 days, and were subsequently exposed to anoxia. Prior to anoxia exposure, Cd concentration was determined in the digestive gland and adductor muscle. After 24 h of anoxia, the activities of pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and cytochrome c oxidase (CCO), and catalase (CAT) were measured in the digestive gland and adductor muscle from Cd-treated mussels. Also, effects of the Cd treatments on the median survival time (LT₅₀) during anoxia were determined. The short-term Cd-exposed mussels augmented the metal uptake in the tested tissues in a dose-dependent manner, associated with a concomitant reduction in the ability to withstand anoxia. During normoxic and anoxic conditions, the Cd-cxposed individuals displayed decreased levels of PK, PEPCK, and CCO in comparison with controls, with the change being most evident during anoxia. Conversely, an increase in CAT was observed in Cd-treated organisms. This effect was further potentiated during anoxia. The toxic action of Cd uptake on PK and PEPCK could reduce the tolerance of anoxia, because these are regulatory glycolytic enzymes in mussels. Moreover, the decreased CCO activity could limit the capacity to recuperate from anoxia. The enhanced CAT activity in Cd-exposed organisms may have been in response to H₂O₂ produced during oxidative stress, and was likely accentuated during anoxia.