Nitric oxide (NO) is a free radical implicated in numerous cell signaling, physiological and pathophysiological processes of eukaryotic cells. Here, we describe the production of NO as part of the cellular stress response of the symbiotic sea anemone Aiptasia pallida, which hosts dinoflagellates from the genus Symbiodinium. We show that exposure to elevated temperatures induces symbiotic anemones to produce high levels of NO, leading to the collapse of the symbiosis. These results shed light on the poorly understood cellular mechanism through which elevated seawater temperature causes the release of symbiotic algae from symbiotic cnidarians, a detrimental process known as coral (cnidarian) bleaching. The results presented here show that the host cell is a major source of NO during exposure to elevated temperatures and that this constitutes a cytotoxic response leading to bleaching. These results have important evolutionary implications as the observed NO production in these basal metazoans displays many parallels to the cytotoxic inflammatory response to pathogens, a well-understood process in mammalian model systems.