Background: By the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was revealed in China and led to a widespread global outbreak and posed a serious threat to public health. The pathophysiology of COVID-19 is heavily reliant on cytokines either beneficial like type I interferon (IFN), or harmful like tumour necrosis factor alpha (TNF-α), considering the so-called cytokine storm. Aim of the study: to assess serum levels of TNF-α & IFN-α in COVID-19 patients and their correlations with disease severity. This might add a new aspect in COVID-19 treatment either cytokine and/or anti-cytokine therapy. Methods: The current study was conducted on 60 patients diagnosed as COVID-19, divided into two groups ICU and non ICU (30 patients each) and 30 apparently healthy individuals. Serum levels of TNF-α and IFN-α were measured by ELISA. Results: There was a statistical significant difference between COVID-19 patients and control group as regards TNFα and INFα serum levels (P<0.001, P<0.001) respectively. Significant correlation between TNF -α, INF-α serum levels and patients outcome ( p =0.000, p =0.000) respectively. Conclusion: Serum level of TNF-α is significantly higher in COVID-19 patients compared to controls while serum level of INF α that is significantly higher in controls compared to COVID-19 patients. Their association with disease severity suggests that they can possibly serve as reliable biomarkers for monitoring disease activity and predicting severity and outcome in COVID-19.