The hypoxia-intolerant rainbow trout (Oncorhynchus mykiss (Walbaum, 1792)) exhibits increased branchial ion permeability and Na+ influx during acute exposure to moderate hypoxia (Po2 = 80 torr; 1 torr = 133.3224 Pa), manifesting the usual trade-off between gas exchange and electrolyte conservation. In contrast, the hypoxia-tolerant oscar (Astronotus ocellatus (Agassiz, 1831)) is unusual in exhibiting decreased branchial ion permeability to ions and Na+ influx during acute exposure to severe hypoxia (Po2 = 10–20 torr). These different physiological approaches to the osmo-respiratory compromise correlate with rapid, oppositely directed changes in gill morphology. In oscar, pavement cells (PVCs) expanded, partially covering neighboring mitochondria-rich cells (MRCs), which were recessed and reduced in size. Those remaining open were transformed from “shallow-basin” to “deep-hole” forms with smaller openings, deeper apical crypts, and smaller numbers of subapical microvesicles, changes that were largely reversed during normoxic recovery. In contrast, moderate hypoxia caused outward bulging of MRCs in rainbow trout with increases in size, surface exposure, and number of subapical microvesicles, accompanied by PVC retraction. These changes were partially reversed during normoxic recovery. In both rainbow trout and oscar, hypoxia caused discharge of mucus from enlarged mucous cells (MCs). Rapid, divergent morphological changes play an important role in explaining two very different physiological approaches to the osmo-respiratory compromise.