NK group 2 member A (NKG2A) receptor transduces inhibitory signaling; suppressing NK and T-cell cytokine secretion and cytotoxic function. This study aimed to assess the expression of NKG2A inhibitory receptor on natural killer (NK) cells and CD8+ T lymphocytes in COVID-19 patients and correlate the results with disease severity defined according to the criteria established by the world health organization, in a trial to understand the immunological response towards COVID-19 infection. The study enrolled 30 COVID-19 patients classified into 2 groups that comprised 15 subjects each; moderate and severe based on clinical, radiological, and laboratory findings. Ten age and sex matched apparently healthy individuals were included in this study as a control group. About 1 ml EDTA anti-coagulated blood samples were collected for measuring expression of NKG2A/CD159a on CD56+ CD3- NK and CD3+CD8+ T cells by flow cytometry. Results revealed that COVID-19 patients had significantly lower NK and CD8+ T cell counts compared to healthy subjects. Severe cases had significantly lower CD8+ T counts compared to moderate ones. Percentages of NK and CD8+T cells expressing NKG2A receptor were significantly higher in cases compared to controls. Comparison between severe and moderate cases revealed that although the percentages of NK cells expressing NKG2A receptor were not significantly higher in severe cases, the mean fluorescence intensity was significantly higher. The percentages of CD8 +T cells expressing NKG2A receptor were significantly higher in severe cases with higher mean fluorescence intensity. In conclusion, our results indicate that elevated NKG2A expression on cytotoxic lymphocytes correlates with disease severity in COVID-19 patients, and may serve as a potential marker for prognosis. Additionally, the blockade of NKG2A should be investigated as means of enhancing NK cell and cytotoxic T cells antiviral immunity in patients with severe COVID-19 infection.