Gut microbiota is an essential element of maintaining the immune homeostasis, including in individuals with COVID-19. The study was aimed to assess taxonomic changes in the gut microbiota and their relationship with the disease severity and the levels of IL6, IL10, IL17, and TNFα in patients with COVID-19. A total of 110 patients with COVID-19 (index group) and 98 individuals with no COVID-19 (control group) were enrolled to the comparative cross-sectional study. The gut micribiota composition was determined by shotgun sequencing. Blood serum levels of IL6, IL10, IL17, and TNFα were assessed by enzyme-linked immunosorbent assay. The following significant changes in the gut microbiota composition were observed in patients with COVID-19 in contrast to controls: decreased abundance of B. adolescentis (p = 0.048), E. rectale (p = 0.036), F. prausnitzi (p = 0.0002), B. dorei (p < 0.001), and increased abundance of R. gnavus (p = 0.012), Сl. hathewayi (p = 0.003), E. faecium (p = 0.0003). Correlations were established between the abundance of B. dorei and the IL6 levels (r = 0.49; p = 0.034), the abundance of F. prausnitzii and the levels of IL10, IL17 (r = 0.44; p = 0.001 and r = –0.52; p < 0.001, respectively). The abundance of R. gnavus correlated with the TNFα levels, and the abundance of E. faecium was related to the levels of IL6 (r = 0.47; p = 0.002) and TNFα (r = 0.56; p = 0.001). The relationship between the abundance of B. dorei, F. prausnitzii, E. faecium and the higher SHOKS-COVID clinical assessment scale scores was also revealed (r = –0.54; p = 0.001, r = –0.60; p < 0.001 and r = 0.67; p = 0.005, respectively). Targeted correction of gut microbiota may improve the COVID-19 treatment efficacy.