Background: Nowadays there are no established laboratory criteria of the high stroke risk in patients with severe atherosclerotic carotid stenosis (ACAS). Aim: to study the information value of laboratory markers in patients with severe atherosclerotic stenosis of the internal carotid artery in the forecast for the development of atherothrombotic stroke. Material and methods. Prospective sampling of atherosclerosis, brain damage and endogenous neuroprotection biomarkers serum levels was performed in 30 patients with acute atherothrombotic stroke/transient ischemic attack and 50—99% ACAS (group 1), 51 patients with severe ACAS without history of vascular events during one month before enrollment (group 2), and 16 healthy volunteers (aged 50—80 years). Results. High-sensitive C-reactive protein (hsCRP) and asymmetric dimethylarginine (ADMA) serum levels were significantly higher in group 1 vs. group 2 and group 3 (p<0,05). Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) and Insulin-like Growth Factor-1 (IGF-1) serum levels were significantly higher in asymptomatic vs. symptomatic stenosis (p<0,05). Phosphorylated Axonal Neurofilament (PNF-H) serum level in group 2 was significantly smaller vs. group 3 and group 1 (p<0,05), Ciliary neurotrophic factor (CNTF) serum level was significantly higher in group 1 and 3 vs. healthy controls (p<0,05). For asymptomatic internal carotid artery stenosis pregnancy-associated plasma protein A (PAPP-A) serum level was ≤0,326 μg/mL and PNF-Н serum level was ≤94,528 pg/ml with classifier cross-validation accuracy 85±14%. Conclusion. ADMA, hsCRP and CNTF serum levels increase and PNF-H level decreases at the atherothrombotic stroke acute phase. Low IGF-1 and IGFBP-3 levels in ACAS patients might indicate an additional stoke risk. Further studies are needed to clarify, whether PAPP-A ≤0,326 μg/mL and PNF-H ≤94,528 pg/ml levels are associated with the conversion of asymptomatic stenosis into symptomatic.