Abstract Lobsters from eastern Long Island Sound (LIS) were exposed to laboratory conditions designed to simulate the habitat in western LIS during the 1999 mass mortality. Elsewhere (Robohm et al. 2005) we have shown that hypoxia and concomitant biogeochemical conditions increase the susceptibility of lobsters to a common pathogen at normal summer temperatures. Here we report that in otherwise favorable conditions, high temperature (24°C) alone had no lethal effect on disease-free eastern LIS lobsters for weeks. However, at this temperature, moderate hypoxia (<2.5 mg/L dissolved oxygen) was lethal to half of a group (n = 20) of lobsters in about 5 days. Addition of sulfide and ammonium to levels reported for LIS (5.5 μM sulfide and 17 μM ammonium) decreased the LT50 to 3.3 days. Higher sulfide concentrations decreased the LT50 significantly. We conclude that lobster survival times are greatly diminished by hypoxia, sulfide and ammonium at high temperature. Because seasonal hypoxia with the production of sulfide and ammonium is an annual occurrence due to cultural eutrophication in western LIS, the results imply that habitat conditions could have been sufficient to account for the observed mortalities in the warm summer of 1999.