Since the outbreak of COVID‐19 in China, it has rapidly spread across many other countries. We evaluated antioxidant defense systems and inflammatory status related to the SARS‐CoV2 infection in a population from southwestern Iran. Comorbidities and clinical symptoms of 104 subjects (comprising negative and positive‐PCR COVID‐19 outpatients) were assessed. Serum concentrations of glutathione reductase (GR) and interleukin‐10 (IL‐10) were measured using ELISA. In the positive‐PCR group, follow‐ups on clinical symptoms were carried out for 28 days at 7‐day intervals. In the positive‐PCR group, hypertension, diabetes, liver disease, chronic heart disease, and chronic kidney disease were the most common comorbidities. In the general category of symptoms, we found a significant difference between negative and positive‐PCR groups, except regarding runny noses. In the pulmonary category, there was a significant difference between the two groups except in terms of chest pain. We also determined a significant difference in neurologic symptoms, except for ear pain, between negative and positive‐PCR groups. We also found significantly lower levels of GR but higher levels of IL‐10 in the positive‐PCR group (p = 0.000 for both). In the positive‐PCR group, serum levels of IL‐10 (odds ratio = 0.914, p = 0.012) decreased the chances of neurological symptoms occurring over time. The antioxidant defense systems of positive‐PCR outpatients failed as demonstrated by a reduction in the serum levels of GR. We also indicated a dysregulation in the immune response against COVID‐19, characterized by changes in serum IL‐10 levels.