Background. COVID-19 is a widespread, important, and frequently fatal disease, considered a risk factor for the development and progression of other pathologies. One of the most common associated conditions is stroke. Objective: to identify the patterns of occurrence and mechanisms of ischemic stroke (IS) development under novel coronavirus infection COVID-19. Patients/Methods. The prospective study included 80 individuals: 20 COVID-19 patients with subsequent IS development (main group); 40 COVID-19 patients without cerebrovascular accident (comparison group); 20 healthy volunteers (control group). Concen-trations of fibrinogen, antithrombin III, D-dimer, von Willebrand factor (vWF), C-reactive protein (CRP), matrix metalloproteinase-2 (MMP-2), cytokines (interleukin, IL) — IL-6, IL-8, IL-10, tumor necrosis factor-alpha (tumor necrosis factor-alpha, TNF-α) were accessed in peripheral blood. The study was carried out from November 2020 to February 2021. The primary endpoint of the study was IS development in COVID-19 patients. Results. In 70% patients of the main group a stroke developed by the end of the second week from the infection onset. The main risk factor in 12 (57%) COVID-19 patients with an unfavorable stroke course and subsequent development of multiple organ failure syndrome (MOFS) was a high comorbidity with various forms of circulatory system pathology. All 12 patients with IS and MOFS (100%) showed a statistically significant changes in many clinical and laboratory parameters by the end of the first day after admission to the hospital: they had arterial hypertension (100%), tachycardia (80%), significant increased blood levels of D-dimer (83%), vWF (75%), IL-10 (92%), TNF-α (92%), CRP (100%), MMP-2 (100%). Conclusions. COVID-19 and high comorbidity with various forms of circulatory system pathology are 2 significant risk factors for both the occurrence and adverse course of stroke and its outcomes. Arterial hypertension, increased blood levels of D-dimer, vWF, IL-10, TNF-α, CRP and MMP-2 are the early predictors of acute MOFS development in more than 75% of COVID-19 patients with stroke. © Kabaeva E.N., Litvitskiy P.F., Artyukov O.P., Tushova K.A., Nozdryukhina N.V., Ershov A.V., 2022