Build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). We investigated brain swelling and its possible relationship to oxidative stress in the brain and liver of goldfish acutely exposed to high external ammonia (HEA; 5 mmol L^-1 NH4Cl) at two different acclimation temperatures (14°C, 4°C). At 14ºC, HEA for 72 h increased internal ammonia and glutamine concentrations caused cellular oxidative damage in brain and liver. However, damage was most pronounced in brain, in which there was a 2-fold increase in thiobarbituric-acid reactive substances, a 3-fold increase in protein carbonylation, and a 20% increase in water volume (indicative of brain swelling). Increased activities of catalase, glutathione peroxidase, and glutathione reductase in the brain, suggested that goldfish upregulate their antioxidant capacity to partially offset oxidative stress during hyperammonemia at 14ºC. Notably, acclimation to colder (4°C) water completely attenuated the oxidative stress response to HEA in both tissues, and there was no change in brain water volume, despite similar increases in internal ammonia. We suggest that ammonia-induced oxidative stress may be responsible for the swelling of goldfish brain during HEA, but further studies are needed to establish a mechanistic link between ROS production and brain swelling. Nevertheless, a high capacity to withstand oxidative stress in response to variations in internal ammonia likely explains why goldfish are more resilient to this stressor than most other vertebrates.