This study determined the respiratory responses to progressive hypoxia in oscar, an extremely hypoxia-tolerant Amazonian cichlid. Oscar depressed oxygen consumption rates (View the MathML source), beginning at a critical O2 tension (Pcrit) of 46 Torr, to only 14% of normoxic rates at 10 Torr. Total ventilation (View the MathML source) increased up to 4-fold, entirely due to a rise in ventilatory stroke volume (no change in ventilatory frequency), and water convection requirement (View the MathML source) increased substantially (up to 15-fold). Gill O2 extraction fell steadily, from 60% down to 40%. Although O2 transfer factor (an index of gill O2 diffusion capacity) increased transiently in moderate hypoxia, it decreased at 10 Torr, which may have caused the increased expired–arterial PO2 difference. Venous PO2 was always very low (≤7 Torr). Anaerobic metabolism made a significant contribution to ATP supply, indicated by a 3-fold increase in plasma lactate that resulted in an uncompensated metabolic acidosis. Respiration of isolated gill cells was not inhibited until below 5 Torr; because gill water PO2 always exceeded this value, hypoxic ion flux arrest in oscars [Wood et al., Am. J. Physiol. Reg. Integr. Comp. Physiol. 292, R2048-R2058, 2007] is probably not caused by O2 limitation in ionocytes. We conclude that metabolic depression and tolerance of anaerobic bi-products, rather than a superior capacity for O2 supply, allow oscar to thrive in extreme hypoxia in the Amazon.