The volume and location of intracranial hematomas are well-known prognostic factors for traumatic brain injury (TBI). The aim of this study was to determine the relationship of serum biomarkers S100β, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), total tau (T-tau), phosphorylated neurofilament heavy chain (pNF-H), serum amyloid A 1 (SAA 1), C-reactive protein (CRP), procalcitonin (PCT), and chitinase-3-like protein 1 (YKL-40) with TBI severity and the amount and location of hemorrhagic traumatic lesions.A prospective observational cohort of 115 patients with Glasgow Coma Scale (GCS) 3-15 was evaluated. Intracranial lesion volume was measured from the semiautomatic segmentation of hematoma on CT using Analyze software. The establishment of possible biomarker cut-off points for intracranial lesion detection was estimated using Youden's Index (J) obtained from the area under the receiver operating characteristic curve (AUROC).SAA 1, YKL-40, PCT and S100β showed the most robust association with level of consciousness, both with total GCS and motor score. Biomarkers significantly correlated with volumetric measurements of subdural (SDH), subarachnoid (tSAH), intraparenchymal (ICH), intraventricular (IVH) and total amount of bleeding. The type of intracranial hemorrhage was associated with various release patterns of neurobiochemical markers.YKL-40, SAA 1, CRP and PCT combined with S100β were the most promising biomarkers to determine the presence, location and extent of traumatic intracranial lesions. Combination of biomarkers further increased the discriminatory capacity for the detection of intracranial bleeding.