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Context Overwhelming post-splenectomy sepsis is defined as septicaemia and/or meningitis, usually fulminant, occurring days to several years after removal of the spleen. We report a case of a fulminant pneumococcal sepsis with a fatal outcome, occurring 11 years after distal pancreatectomy and splenectomy for pancreatic adenocarcinoma. Case report A 58-year-old woman presented to the emergency room in December 2011 with a 2-day history of mild fever and diarrhea, followed by hypotension, dyspnea, and peripheral cyanosis. Past medical history revealed a left breast quadrantectomy for lobular carcinoma, and distal pancreatectomy with splenectomy for ductal pancreatic adenocarcinoma in October 2000. The patient was not aware of the need for prophylactic antibiotics and vaccination after splenectomy. At admission, blood tests revealed abnormal coagulation screen, abnormal liver and kidney function, and metabolic acidosis. Despite the administration of intravenous fluid, vasopressor agents, antibiotics and mechanical ventilatory support, the patient died for multiorgan failure 7 hours after admission in intensive care unit. Blood culture showed the growth of Streptococcus pneumonia. Necropsy showed multiorgan failure with adrenal necrotic hemorrhage due to pneumococcal septicemia. No recurrence of pancreatic cancer was noted. Conclusions Overwhelming post-splenectomy sepsis is a well-known fatal complication which can occur in asplenic patients. The role of vaccination and antibiotics in preventing such complication is well-defined, but cases of fatal post-splenectomy sepsis are still reporting, also in vaccinated patients. High index of suspicion must be maintained for any febrile illness in asplenic patients.