Traumatic brain injury (TBI) is a common neurological disorder, with 2.5 million new cases reported annually in Europe. Mild TBI (mTBI) accounts for 80–90% of cases and presents diagnostic challenges, particularly in children, whose immature nervous systems are highly vulnerable. Identifying intracranial injuries (ICIs) while minimizing unnecessary interventions remains a key challenge. This thesis investigates the use of blood biomarkers to improve mTBI management, particularly in pediatric patients. A multicenter study was conducted in Switzerland and included 600 children. Blood concentrations of eight proteins were measured by immunoassays. GFAP, HFABP, and S100b showed 100% sensitivity in excluding ICIs, with a specificity of 30%. The cytokine IL6 demonstrated higher specificity, reaching 61% when combined with brain biomarkers. Further studies in adults also explored inflammatory responses linked to long-term outcomes after TBI. A two-biomarker signature (IL15 and MCP1) was found to be significant. Overall, blood biomarkers, especially IL6, offer a promising non-invasive tool for TBI management, warranting further large-scale validation.