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Background: The aim of this case report is to discuss diagnostic workup and clinical management of cytomegalovirus reactivation in a critically ill immunocompetent pediatric patient., Case Presentation: A 2-year-old white boy who had no medical history presented with respiratory distress and fever. His Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores were 20 and 11, respectively. Our preliminary diagnosis was multiple organ dysfunction secondary to sepsis. Antibiotic treatment was started; he was intubated and artificially ventilated. Norepinephrine infusion was started. Hemophagocytic lymphohistiocytosis was diagnosed because our patient had elevated levels of serum ferritin, bicytopenia, splenomegaly, fever (> 38.5 °C), and hemophagocytosis shown in a bone marrow sample. Therapeutic plasma exchange and intravenously administered high-dose corticosteroid for hemophagocytic lymphohistiocytosis and continuous renal replacement treatment for acute renal failure were initiated. Following 5-day high-dose corticosteroid administration, therapeutic plasma exchange, and continuous renal replacement treatment, his clinical status and kidney and liver functions improved, and vasoactive requirement and ferritin levels decreased. He was extubated on the seventh day. On the tenth day of hospitalization he had a seizure and was diagnosed as having septic encephalopathy. His immune functions were found to be normal. Although his medical condition improved continuously, he had left spontaneous pneumothorax on the 21st day of admission as a complication of necrotizing pneumonia. Since pneumothorax persisted, left upper lobectomy surgery was performed on the 30th day of hospitalization. In the pathological examination of the excised lung tissue, features of cytomegalovirus infection were observed. Ganciclovir treatment was started. Serological tests indicated that our patient had cytomegalovirus reactivation. Antiviral treatment was stopped after 17 days, when cytomegalovirus deoxyribonucleic acid (DNA) polymerase chain reaction results became negative. He fully recovered and was discharged on the 50th day of admission., Conclusions: Cytomegalovirus reactivation in critically ill patients is a prevalent problem and shown to be associated with higher mortality and morbidity. In a case of serologic detection of cytomegalovirus reactivation without any clinical sign of infection, pre-emptive treatment could be considered with assessment of risks and benefits for each patient. Antiviral therapy is highly recommended for patients who have risk factors identified.