Introduction. COVID-19 and long COVID (LC) are often accompanied by neurological disorders. The precise mechanisms of LC brain dysfunction remain unclear. A comparative study of circulating biomarkers in patients with COVID-19 and neurodegenerative diseases (NDD) may help elucidate the mechanisms of neuroinflammation in COVID-19. The аim of this study was a comparative analysis of circulating biomarkers in patients with COVID-19 and NDD: Alzheimer’s disease and Parkinson’s disease. Material and methods. The study involved four groups of patients with: LC accompanied with neurological symptoms (n = 36); Alzheimer’s disease (n = 40); Parkinson’s disease (n = 44); healthy donors (n = 30). The level of sCD40L, MDC, fractalkine, IP-10 and GFAP proteins in the serum samples was determined using enzyme-linked immunosorbent assay. The statistical methods for processing of the results involved the Kruskal–Wallis and Mann– Whitney tests, orthogonal principal component analysis and linear discriminant analysis. Results. Both common changes in the levels of the studied markers in all groups compared to the сomparison group (increased GFAP and VEGFA levels) were identified in patients with COVID-19 and NDD, as well as specific differences unique to COVID-19 (low MDC and sCD40L levels). Conclusion. The study revealed significant differences in the concentrations of the biomarkers studied between COVID-19 patients and patients with NDD and the сomparison group. Elevated GFAP level most significantly aligns the pathophysiology of COVID-19 with NDD, while results of comparison of levels of other biomarkers highlight how its profile in this acute infectious disease differs from profiles of Alzheimer’s disease and Parkinson’s disease.