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In hypoxia, air-breathing fish obtain O₂from the air but continue to excrete CO₂into the water. Consequently, it is believed that some O₂obtained by air-breathing is lost at the gills in hypoxic water.Pangasionodon hypophthalmusis an air-breathing catfish with very large gills from the Mekong River basin where it is cultured in hypoxic ponds. To understand howP. hypophthalmuscan maintain high growth in hypoxia with the presumed O₂loss, we quantified respiratory gas exchange in air and water. In severe hypoxia (PO₂: ≈ 1.5 mmHg), it lost a mere 4.9% of its aerial O₂uptake, while maintaining aquatic CO₂excretion at 91% of the total. Further, even small elevations in water PO₂rapidly reduced this minor loss. Charting the cardiovascular bauplan across the branchial basket showed four ventral aortas leaving the bulbus arteriosus, with the first and second gill arches draining into the dorsal aorta while the third and fourth gill arches drain into the coeliacomesenteric artery supplying the gut and the highly trabeculated respiratory swim-bladder. Substantial flow changes across these two arterial systems from normoxic to hypoxic water were not found. We conclude that the proposed branchial oxygen loss in air-breathing fish is likely only a minor inefficiency.