Purpose <p>Traumatic brain injury in children can lead to lifelong sequelae and disabilities. Identifying the mediators of the neuroinflammatory process resulting from head trauma is of great importance. We therefore explored the plasma levels of neurogenic inflammatory and vasodilator peptides in children with head trauma and their relationship with the clinical characteristics of the patients.</p> Methods <p>Forty head-traumatized and 26 healthy children aged 2 months–7 years old were prospectively enrolled in the study. Demographic characteristics of patients and controls were recorded. Glasgow coma score (GCS), cause of trauma, computed tomography (CT) results, blood pressure, and pulse rate were recorded. Plasma calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), vasoactive intestinal peptide (VIP), and substance P (SP) levels of patients and controls were measured by ELISA. Correlation and ROC analyses were carried out.</p> Results <p>The mean GCS of the patients was 14.8 ± 0.4, which was in the mild traumatic brain injury (mTBI) category. Plasma levels of CGRP, PACAP-38, VIP, and SP in patients with head trauma were significantly higher than controls. All peptide levels were significantly higher in CT-positive patients than in CT-negative patients who had only head trauma. Only CGRP was higher in female patients than in the males. A positive correlation was found between CGRP, PACAP-38, and SP levels, as well as between PACAP-38 and VIP. ROC analysis detected that these peptides had a diagnostic value in mTBI.</p> Conclusion <p>Evaluation of pediatric patients with head trauma together with these neuropeptides may provide great benefits in deciding whether to perform radiography such as CT. However, due to the relatively low sensitivities in ROC analysis and small sample size, further studies are warranted before they may be used as a screening test to distinguish CT-positive from CT-negative patients.</p>