The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now causing a pandemic with a rapid spread and become a global public health problem. Coronavirus illness-2019 is a potentially lethal disease, especially for patients with comorbidities. Natural killer (NK) cells are important in controlling the immunological response in COVID-19 patients, but their effector capabilities are disturbed in those with comorbidities. Preliminary research in COVID-19 patients with severe illness reveals a drop in NK cells quantity and activity, leading to a decrease in the clearance of infected and activated cells and an unregulated rise in tissue-damaging inflammatory markers. Knowing the mechanism and role of NK cells in COVID-19 becomes necessary for better understanding and treatment of COVID-19.