A 21-month-old boy was seen in the emergency department (ED) for a 3-day history of nausea, vomiting and diarrhea. He had more than 30 bowel movements the day prior. He was discharged with recommendations to increase oral fluid intake and ondansetron as needed. Symptoms persisted and he returned 2 days later to the ED with systemic symptoms and abnormal laboratory studies concerning for HUS secondary to Escherichia coli. Intravenous fluids and continuous renal replacement therapy were started. Acute clinical decline led to Pediatric intensive care unit admission the next day. One day later, he developed altered mental status with fixed and dilated pupils. Computerized tomography of the head showed mild pneumocephalus in the left hemispheric convexity. Within a span of 4 hours, the infection spread to the majority of the left cerebral hemisphere despite starting piperacillin/ tazobactam and meropenem. 7 hours later, there was generalized loss of brain parenchyma. Cerebrospinal fluid cultures showed Clostridium septicum. Autopsy revealed pneumocephalus secondary to Clostridium septicum.