Widespread coral bleaching and mortality, leading to coral reef decline, have been mainly associated with climate-change-driven increases in sea surface temperature. However, bleaching and mortality events have also been related to decreases in sea surface temperature, with cold stress events (e.g. La Niña events) being expected to increase in frequency or intensity as a result of a changing climate. Cold stress creates physiological symptoms in symbiotic reef-building corals similar to those observed when they are heat stressed, and the biochemical mechanisms underpinning cold stress in corals have been suggested to be related to an oxidative stress condition. However, up to now, this hypothesis had not been tested. This study assessed how short and long cold excursions in seawater temperature affect the physiology and biochemical processes related to oxidative stress in the reef-building coral Stylophora pistillata. We provide, for the first time, direct evidence that the mechanisms underpinning cold stress and bleaching are related to the production of reactive oxygen species, and that rapid expulsion of a significant proportion of the symbiont population by the host during cooling conditions is an acclimation mechanism to avoid oxidative stress and, ultimately, severe bleaching. Furthermore, this study is one of the first to show that upwelling conditions (short-term cold stress+nutrient enrichment) can provoke a more severe oxidative stress condition in corals than cold stress alone.