Introduction. Recent work demonstrates that HIF-1α and NOS isoforms are detectable in plasma, representing their potential practical relevance as biomarkers. At the same time, data on the stability of these proteins in plasma are contradictory. Aim of the study. To investigate the amount of HIF-1α and iNOS in plasma of patients with COVID-19 infection of different severity to assess the possi-bilities of adaptation to hypoxia. Material and methods. The pilot study involved 50 patients divided into three groups: 1) 17 patients with moderate severity of the disease; 2) 17 pa-tients in severe condition; 4) 16 patients with extremely severe course of the disease. The amounts of HIF-1α and iNOS were determined by competi-tive ELISA. Results. Patients with extremely severe course of COVID-19 infection showed lower levels of HIF-1α and blood saturation compared to the moderate and severe course groups. The iNOS levels were significantly lower in the extremely severe course group compared to patients with moderate disease severity. When patients were evaluated according to the degree of lung damage based on CT scans, reduced HIF-1α levels were identified in the CT-3-4 group compared to the CT-0-1 (p = 0.0006) and CT-2 (p = 0.0031) groups. Conclusions. Decreased levels of HIF-1α and iNOS in extremely critically ill patients may serve as an unfavorable prognostic marker