This case series describes multiple mortalities associated with sepsis, neoplasia, and endoparasitism in yellow-lipped sea kraits (Laticauda colubrina) at an exhibit aquarium. Over a 2-yr period, the facility kept 42 L. colubrina, of which 38 died and 19 were suitable for necropsy and histopathology. The common clinical syndrome seen in these animals consisted of partial to compete anorexia, increased time spent “hauled-out” on land, intermittent regurgitation, chronic lethargy, and weight loss. Few animals died without premonitory signs. Nutritional support and treatment for presumptive parasitism and sepsis were unsuccessful. The mortality seen in this collection of sea kraits could be placed into three groups; one group of animals (n = 9) died of sepsis secondary to necrotizing enteritis or pneumonia; one group (n = 6) remained apparently healthy for over 1 yr and then died with multifocal granulomas and sepsis; and the last group (n = 3) died as a result of multicentric lymphoid neoplasia with secondary sepsis. The unifying factor in the majority of these cases is the presence of septicemia as the proximate cause of death. Based on the clinical picture, it is presumed that an immunosuppressive event, such as transport, captivity stress, or possible concurrent viral infection, resulted in a septic event and death.