Coronavirus disease-2019 (COVID-19), a respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health emergency and a threat the entire world. The COVID-19 shows a wide spectrum of clinical presentations, severity, and fatality rates. Although the fatal outcomes of the COVID-19 pandemic are evident in all age groups, the most devastating impact on the health consequences and death from COVID-19 are associated with older adults, especially older men. COVID-19 pandemic is affecting different countries in the world especially in the 65+ years age male group. In fact, several genes involved into the regulation of the immune system are strategically placed on the X-chromosome and trigger a gendered mediated antiviral fight. The aim of this study is to explore and exploit whether a relationship exists between male sex and COVID-19 mortality and the relationship is age dependent. Herein we discuss the possible role of physiological and immunological sex differences into the higher morbidity and mortality of SARS-CoV-2 between females and males. Deciphering gender differences in COVID-19 offers a window into the principles of immunity against SARS-CoV-2 infection and this information on ageing dependent gender disparity might contribute to our current understanding of COVID-19 infection and disease treatment.