The pathogenesis of SARS‐CoV‐2 infection, causative pathogen of the known COVID‐19 pandemic is not well clarified. In this regard oxidative stress is one of the topics that need to be investigated. Therefore, the present research was performed to explore the relationship between the oxidant/antioxidant system and COVID‐19 exacerbation. Sera were collected from 120 patients with COVID‐19 infection and 60 healthy volunteers as the control group. The patient group consisted of 60 cases with mild disease and 60 severely ill patients. Serum levels of total antioxidant capacity (TAC) and nitric oxide (NO) as well as serum activities of the two main antioxidant defense enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured. TAC levels were considerably lower in patients compared with healthy individuals (p < 0.05) and also between patients with mild and severe diseases (p < 0.05). A rather decreasing trend was also found in NO concentration as well as SOD and CAT activity, though, the observed differences were not statistically significant (p > 0.05). These findings suggest that COVID‐19 patients may be susceptible to depleted total antioxidant capacity. Moreover, showing such variations in blood samples of infected individuals could be considered as a predictive marker of COVID‐19 severity.