BACKGROUND: Therapeutic plasma exchange (TPE) removes circulating pathogenic antibodies, immune complexes, cytokines, and complement components. While established in adult neurology, evidence on its safety and efficacy in pediatric neurocritical care remains limited. OBJECTIVE: To evaluate the indications, clinical efficacy, and safety of TPE in children with acute or subacute immune-mediated neurological disorders admitted to the pediatric intensive care unit (PICU). METHODS: A retrospective cohort of 24 pediatric patients (aged 1-18 years) treated with TPE between February 2023 and October 2025 was analyzed. Diagnoses included multiple sclerosis (n = 8), Guillain-Barré syndrome (n = 5), acute disseminated encephalomyelitis (n = 3), transverse myelitis (n = 3), autoimmune encephalitis (n = 3), optic neuritis (n = 1), and myasthenia gravis (n = 1). Patients received 3-7 TPE sessions. Clinical response was measured using the modified Rankin Scale (mRS) and GBS disability scores before and after treatment. RESULTS: A total of 130 sessions were performed. Clinical improvement occurred in 20 of 24 patients (83%)-moderate in 8 (33%) and mild in 12 (50%). Median mRS/GBS scores decreased from 4.0 to 3.0 (p = 0.001). Early initiation of TPE (≤ 7 days from symptom onset) was associated with a higher likelihood of neurological improvement in multivariable analysis. No life-threatening complications were observed. Transient, reversible events included hypocalcemia (2.3%), hypotension (1.5%), and urticaria (1.6%). CONCLUSION: TPE appears to be a safe and potentially beneficial intervention for severe or refractory pediatric neuroimmunological disorders. Earlier initiation of TPE was associated with improved neurological outcomes; however, these findings should be interpreted cautiously given the small sample size and heterogeneous disease groups. These findings support integrating TPE into multidisciplinary PICU management and add to the growing evidence supporting its use in pediatric neuroimmunology.