Introduction <p>The prevalence of child and adolescent obesity has increased globally. Research has associated obesity-induced immune dysregulation with neurological autoimmune diseases. This study investigated whether obesity-driven inflammation and immunomodulation increase the risk of neuroinflammatory diseases in children and adolescents.</p> Methods <p>This retrospective cohort study collected deidentified data from individuals aged 6–18 years from the TriNetX platform. The study cohort was stratified by body mass index (BMI). The outcome measure was the incidence of neuroinflammatory diseases. Covariate-adjusted cox proportional-hazards models were used to assess neuroinflammatory disease risk across the BMI groups.</p> Results <p>Children and adolescents with obesity (BMI: 85th–95th percentile range) and those with severe obesity (BMI: 95th–100th percentile range) had 1.76- and 1.90-fold higher risks of multiple sclerosis (MS), respectively, than did their normal-weight peers. Subgroup analysis revealed that girls and adolescents (age: 12–18 years) were particularly susceptible to MS. The risk of acute disseminated demyelination was elevated in children with obesity but not in those with severe obesity. Notably, no significant association was observed between obesity and myasthenia gravis, inflammatory polyneuropathy, or inflammatory myositis.</p> Conclusion <p>Our findings associate child and adolescent obesity with MS; the associations are likely mediated by systemic inflammation and immune dysregulation. The absence of significant associations between child and adolescent obesity and other neuroinflammatory diseases suggests disease-specific mechanisms, underscoring the need for targeted interventions to mitigate the neurological effects of obesity. Overall, child and adolescent obesity significantly modulate immune function, increasing the risk of certain autoimmune neurological diseases, particularly MS. Early interventions are crucial for reducing long-term health risks.</p>