The global pandemic of COVID-19 has been over four years, and the role of intestinal microbiota in the occurrence and development of COVID-19 needs to be further clarified. During the outbreak of SARS-CoV-2 Omicron variant in China, we analyzed the intestinal microbiome in fecal samples from inpatients with pneumonia and normal individuals in January 2023. The microbiota composition, alpha diversity, beta diversity, differential microbial community, co-occurrence networks, and functional abundance were analyzed. The results showed significant differences in microbiota composition between the two groups. In pneumonia group, the abundance of Bifidobacterium, Blautia, Clostridium and Coprococcus decreased, while the abundance of Enterococcus, Lactobacillus and Megamonas increased. Through LEfSe analysis, 37 marker microbiota were identified in pneumonia group. Co-occurrence network analysis found that Lachnospiraceae was critical for the interaction of intestinal microbiota, and the anti-inflammatory bacteria Blautia was negatively correlated with the pro-inflammatory bacteria Ruminococcus. Functional prediction found the up-regulation of steroid biosynthesis, geraniol degradation and mRNA surveillance pathway in pneumonia group. In conclusion, opportunistic pathogens increased and probiotics or short-chain fatty acid-producing bacteria decreased in the intestinal microbiota of pneumonia inpatients during Omicron epidemic. Blautia could be used as a probiotic in the treatment of pneumonia patients in the future.© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.