Mass mortality events (MMEs) can remove up to 90% of individuals in a population, and are especially damaging to population viability of long-lived species with slow life histories. Our goal was to elucidate the cause(s) of a MME of 53 Blanding’s turtles (Emydoidea blandingii (Holbrook, 1838)), a globally endangered species, in a protected area. We investigated disease, winter-kill, and depredation as potential causes of the mortality. The turtle carcasses lacked soft tissue to test for disease, so we examined tissue from co-occurring live leopard frogs (Lithobates pipiens (Schreber, 1782)) and found no evidence of ranavirus, indicating that the disease was not present at our study site. Water temperature and dissolved aquatic oxygen at known overwintering sites and sites which yielded carcasses did not differ, suggesting that winter-kill did not cause the MME. Carcass condition, comparisons to descriptions of turtle depredation events in the literature, and trail cameras paired with turtle decoys, identified potential predators within the study site, and suggested that mass depredation, enabled by low water levels and a concomitant reduction in aquatic habitat, was the most likely cause of mortality. Our study can inform conservation of the study population and the management of MMEs of long-lived species elsewhere.