Introduction: Sepsis or septic shock, a life-threatening condition, is rarely reported as the initial manifestation of uterine malignancy. Case report: A 43-year-old woman consulted our hospital for pyrexia, anorexia, dyspnea, and a markedly distended abdomen. Computed tomography images showed a large abdominal tumor occupying almost the entire abdominal cavity with an air-fluid level and multiple masses in both lungs. Pelvic examination revealed necrotic tissues with blood, prolapsing from the uterus, and having a putrid odor. Her vital signs indicated a systemic inflammatory response syndrome. Antibiotic, anti-shock, and anti-disseminated intravascular coagulation therapies were administrated, but the patient died of multiple organ failure at 22 hours after admission. Autopsy and histopathological examination revealed that the giant abdominal mass was a uterine leiomyosarcoma, in which the myometrium was extensively necrotic with a putrid odor. The patient’s blood culture was positive for Escherichia coli, and sepsis and septic shock due to intrauterine infection of the uterine leiomyosarcoma was considered as the cause of death. Conclusions: Physicians should be aware that uterine malignancy could present as sepsis in women with an abdominal mass.