Global climate change and anthropogenic activities are threatening the future survival of coral reef ecosystems. The ability of reef-building zooxanthellate coral to survive these stressors may be determined through fundamental differences within their symbiotic dinoflagellates (Symbiodinium sp.). We define the in vitro apoptotic response of 2 evolutionarily distant Symbiodinium sp., subtypes B2 and C1, to determine the synergistic effects of disease and temperature on cell viability using flow cytometry. The putative yellow band disease (YBD) consortium of Vibrio spp. bacteria and temperature (33°C) had a positive synergistic effect on C1 apoptosis, while B2 displayed increased apoptosis to elevated temperature (29 and 33°C), the Vibrio consortium, and a lone virulent strain of V. alginolyticus, but no synergistic effects. Additionally, heat shock protein 60 expression revealed differential cell-mediated temperature sensitivity between subtypes via western blotting. This result marks the first evidence of Symbiodinium sp. apoptotic variations to YBD pathogens and emphasizes the potential impact of synergistic stress on globally distributed coral-Symbiodinium symbioses.