Abstract We present an unusual case of a 31-year-old nulliparous woman who was in her normal state of health until 3 weeks before her Emergency Department visit, when she began to have generalized abdominal pain that got acutely worse over a few days. She had a soft abdomen, but complained of excruciating pain. Her computed tomography (CT) scan revealed thrombosis in the superior mesenteric, splenic, and portal veins. Her hematological work-up detected a protein S deficiency, which is associated with recurrent venous thrombosis. The finding of mesenteric venous thrombosis associated with protein S deficiency is rare. The most important factor in survival is early diagnosis and prompt treatment with anticoagulants. Properly treated, patients with mesenteric venous thrombosis should have a good long-term prognosis. Past medical or family history of thrombosis in combination with abdominal symptoms should increase the suspicion for the disease.