<p>Aquatic acidification presents an ionoregulatory challenge for freshwater teleost fishes. Zebrafish (<i>Danio rerio</i>) exposed to acidic water experience increased loss of Na⁺ and respond with increases in ionocyte abundance. Although this response is presumed to increase Na⁺ uptake, countering the elevated passive Na⁺ loss, it may also increase the water-to-blood diffusion distance, thereby impairing gas transfer. Acidic water is also expected to thicken the gill epithelium, which will reduce branchial Na⁺ loss but increase the water-to-blood diffusion distance, a trade-off known as the osmorespiratory compromise. The present study tested the hypothesis that zebrafish reared in acidic (pH 4) water experience reduced hypoxia tolerance owing to the morphological changes elicited by acidic water. Indicators of ionic regulation, gill morphology, hypoxia tolerance and ventilation were measured at 6, 15, 30 and 90 days post-fertilization (dpf). Fish reared in pH 4 water generally had significantly higher whole-body Na⁺ concentrations, greater ionocyte abundances in the skin (6 dpf) or gills (15, 30 and 90 dpf), and thicker gills than fish reared under control conditions. These differences were accompanied by higher critical PO₂ (<i>P</i>_<i>crit</i>) values at 6, 15 (<i>p</i> = 0.066) and 90 dpf, a response consistent with reduced hypoxia tolerance. In adults, the hypoxic ventilatory response was blunted in fish raised in acidic water and thus may have contributed to the higher <i>P</i>_<i>crit</i>. However, in larvae, the peak increases in breathing frequency (<i>f</i>_<i>g</i>) during hypoxia were unaffected (6 dpf) or increased (15 dpf) in fish reared at low pH. Collectively, these results demonstrate that rearing in acidic water impairs hypoxia tolerance at select developmental stages in zebrafish.</p>