Herpes simplex encephalitis (HSE) is a severe central nervous system infection with significant morbidity and mortality. While rare, reactivation of HSE following neurosurgical procedures is increasingly reported, particularly in patients with a previously clinically significant HSE, which is the most critical risk factor for reactivation. This case highlights the challenges of managing HSE reactivation risk in pediatric patients with a history of HSE, who are considered high risk due to their susceptibility to viral reactivation. As demonstrated in a nine-year-old girl with intractable epilepsy who underwent corpus callosotomy, postoperative day seven was marked by fever, altered consciousness, and seizures. Delayed antiviral therapy led to severe neurological sequelae. Identified risk factors included perioperative steroid use and surgical stress, with the history of HSE standing out as the predominant risk factor. This case underscores the importance of defining high-risk groups, specifically patients with a prior history of HSE, and proactively managing their care, including consideration of prophylactic antiviral therapy. Early recognition, timely intervention, and comprehensive perioperative strategies are essential to mitigating the risk of severe outcomes in this vulnerable population.