The COVID-19 pandemic has revealed sex-based differences in anti-viral responses, with a higher rate of SARS-CoV-2 infections as well as a higher rate of morbidity and mortality in men than in women. Males and females also show disparate immune responses to COVID-19 infection, which may be important contributors to lower rates of infection, disease severity and deaths in women than in men. Here, the authors review sex differences in SARSCoV- 2 infections, anti-viral immunity and vaccine responses, putting forth the importance of sex, the underappreciated variables in vaccine response and disease infectivity.