Abstract Background Bacterial meningitis (BM) is a life-threatening central nervous system infection with potential for severe neurological sequelae. High mobility group box 1 (HMGB1) is known as a late inflammatory mediator associated with lethal pathology. This study aims to investigate the serial cerebrospinal fluid (CSF) concentrations of HMGB1 in children with BM and its relationship to neurological prognosis. Methods This retrospective cohort study included children with BM, aseptic meningitis (AM), and controls. CSF samples were collected serially from patients with BM and once from those with AM and controls. HMGB1 and interleukin-6 (IL-6) concentrations were measured using ELISA and bead-based multiplex assays, respectively. Statistical analyses included Mann–Whitney U tests, Kruskal–Wallis tests, and three-way ANOVA to evaluate differences among groups and over time. Results HMGB1 levels in the CSF of children with BM were significantly higher than in those with AM and controls (p