AbstractBackground and AimsSARS‐CoV‐2, as a new pandemic disease, affected the world. Short‐chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids are the main metabolites of human gut microbiota. The positive effects of SCFAs have been shown in infections caused by respiratory syncytial virus, adenovirus, influenza, and rhinovirus. Therefore, this study aimed to evaluate the concentration of SCFAs in patients with SARS‐CoV‐2 compared with the healthy group.MethodsThis research was designed based on a case and control study. Twenty healthy individuals as the control group and 20 persons admitted to the hospital with a positive test of coronavirus disease (COVID‐19) real‐time polymerase chain reaction were included in the study as the patient group from September 2021 to October 2021, in Tabriz, Iran. Stool specimens were collected from volunteers, and analysis of SCFAs was carried out by a high‐performance liquid chromatography system.ResultsThe amount of acetic acid in the healthy group was 67.88 ± 23.09 μmol/g, while in the group of patients with COVID‐19 was 37.04 ± 13.29 μmol/g. Therefore, the concentration of acetic acid in the patient group was significantly (p< 0.001) lower than in the healthy group. Propionic and butyric acid were present in a higher amount in the control group compared with the case group; however, this value was not statistically significant (p> 0.05).ConclusionThis study showed that the concentration of acetic acid as the metabolite caused by gut microbiota is significantly disturbed in patients with COVID‐19. Therefore, therapeutic interventions based on gut microbiota metabolites in future research may be effective against COVID‐19.