The study of the clinical features of the course of neonatal sepsis depending on the level of C-reactive protein and presepsin in the dynamics makes it possible to distinguish a cohort of children with a «severe» course of sepsis, who require complex monitoring of life-supporting functions. Purpose - to study the clinical features of the course of neonatal sepsis and to distinguish the signs of «severe» sepsis for the purpose of an individualized approach to the choice of treatment tactics. Materials and methods. 56 medical records of newborns with neonatal sepsis were analyzed. Depending on the level of the inflammatory response, two observation groups were formed. The clinical Group I included 25 patients with neonatal sepsis with a level of C-reactive protein (CRP) <20 mg/l (boys - 52.0%, city residents - 80.0%). The Group II was formed by 31 newborns with sepsis, in whom the content of CRP in the blood was >20 mg/l (boys - 62.8% (p>0,05), city residents - 57.1% (p>0,05)). The content of presepsin in the blood serum of newborns of both comparison groups exceeded 300 pg/ml. According to the main clinical characteristics, these groups were comparable. According to the time of manifestation of clinical signs of sepsis, the distribution by groups was gomogenous. Results. A comprehensive clinical examination of newborns with neonatal sepsis on the 1st and the 3rd day of treatment gave reason to believe that signs of organ dysfunction are not associated with the severity of acute-phase indicators of the immunological response. However, on the 7th day of treatment, in patients with higher indicators of the inflammatory response, the preservation of signs of organ dysfunction, namely certain neurological, respiratory, hemodynamic disorders, changes in nutritional status, were noted. Conclusions. A comprehensive clinical examination of newborns with neonatal sepsis in the dynamics revealed that the preservation of more pronounced signs of organ dysfunction is inherent in patients with higher inflammatory response rates on the 7th day of inpatient treatment. Based on the obtained data, it is shown that the cohort of children with neonatal sepsis was heterogeneous with certain characteristic features depending on immunological reactivity. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the parents was obtained for the research. No conflict of interests was declared by the authors.