Background: COVID-19 (coronavirus disease 2019) was declared as a pandemic by the World Health Organization (WHO) in early 2020. The spectrum of clinical symptoms of COVID-19 patients, including asymptomatic and symptomatic cases, includes dry cough, fatigue, fever, shortness of breath, and gastrointestinal symptoms. However, increased immune inflammatory responses to stimuli could result in overProduction of Pro-inflammatory cytokines, immunopathological complications, and death in patients with COVID-19. Given the anti-inflammatory effects of naProxen, this study aimed to evaluate the effect of naProxen on IL-1β, TNF-α, IL-6, IFN-γ, and TGF-β in COVID-19 patients. Materials & Methods: Serum levels of IL-1β, TNF-α, IL-6, IFN-γ, and TGF-β were determined by a commercial ELISA (enzyme linked immunosorbent assay) kit before and after naProxen treatment. Findings: According to the results, serum levels of IFN-γ and TGF-β cytokines significantly decreased in patients after treatment with naProxen. In addition, naProxen treatment was effective in reducing the serum levels of IL-6 and IL-1β in patients with COVID-19; however, it did not significantly change the serum level of TNF-α. Conclusion: Overall, the findings demonstrated the effectiveness of naProxen on regulating the serum levels of Pro-inflammatory cytokines in COVID-19 patients.