COVID-19, caused by the SARS-CoV-2 virus, has led to a global pandemic with variable clinical manifestations and severity, including respiratory complications. This study aimed to explore the associations between gut microbiota composition and COVID-19 severity while considering patient sex. We analyzed 117 fecal samples from COVID-19 patients obtained from the NCBI database. 16S rRNA gene amplicon analysis was performed via the DADA2 pipeline. Patients were categorized based on disease severity (mild, moderate, or severe) and sex. Alpha diversity and beta diversity (Bray‒Curtis distance) analyses were conducted, along with comparing the relative abundances of bacterial phyla and genera between groups. We revealed significant differences in the gut microbiota composition in terms of COVID-19 severity and sex. Severe cases presented a decrease in the genera Faecalibacterium and Roseburia. Notably, compared with women, men with severe cases presented a significant decrease in these genera. Additionally, a significant increase in Phascolarctobacterium and Methanobrevibacter was observed in severe cases. Alpha and beta diversity analyses did not reveal significant differences according to severity. These results suggest that the gut microbiota composition is associated with COVID-19 severity, with variations based on sex. Previous studies have reported similar microbiota alterations in COVID-19 patients. The underlying mechanisms of these associations remain to be elucidated but may involve microbiota-modulated immune responses. Future therapeutic interventions, such as the use of probiotics or prebiotics to restore a balanced gut flora, should be explored. Furthermore, the influence of sex on COVID-19 severity and the observed differences in microbiota composition between men and women warrant attention in developing sex-specific treatments. Integrating multi-omics data and conducting longitudinal studies on post-COVID-19 cohorts could provide a deeper understanding of the interactions between the gut microbiota and the host, enhancing patient care and strengthening our resilience to future pandemics. This study confirms the importance of the sex-based gut microbiota composition in the progression and severity of COVID-19. A better understanding of these associations could pave the way for targeted therapeutic approaches and precision medicine for COVID-19 patients.