Background. Saccharomyces cerevisiae is one of the microorganisms commonly used as a probiotic. Although it is primarily known as non-pathogenic, it may cause fungemia, particularly in immunocompromised patients or children with a history of long-term hospital stay. Case. A 6-month-old boy with a history of ventriculostomy, ventriculoperitoneal shunt implantation, and external drainage due to an intracranial mass and hydrocephalus was admitted to the pediatric intensive care unit (PICU) on postoperative day 14 due to respiratory distress and intubated on admission. He was started on broad spectrum antibiotics on day 25 of the admission due to fever and clinical deterioration. Culture of the central venous catheter (CVC) yielded S. cerevisiae, the CVC was removed, and the patient was started on caspofungin. We noticed that a patient near this patient was on a probiotic preparation containing S. boulardii for diarrhea before PICU admission. His fever subsided on day 2 of caspofungin, and laboratory findings normalized on follow-up. Conclusions. Probiotics should not be used in PICUs because of the high risk for CVC-related sepsis in critically ill children.