An understanding of the influence of sex (biological attributes) and gender (socially constructed roles, behaviours, expressions, identities) factors on the risk of infection, hospitalization and death is of urgent importance in the COVID-19 pandemic response effort. Despite similar global rates of infection with Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2, the virus responsible for the COVID-19 pandemic), hospitalizations and mortality are higher in men than in women. Females may be less vulnerable to viral infection due to sex-based differences in immune responses and renin-angiotensin system activity. The response and side effects of currently studied potential therapies for COVID-19, such as hydroxychloroquine, likely differ by sex. Women form the majority of the health care workforce and a uniform approach to sizing of personal protective equipment may provide differing levels of protection from viral infection to health care workers of varying shapes and sizes. Important gender differences exist in the response to public health measures to prevent and contain spread of COVID-19, as well as presentation for testing and medical care, which may inadvertently propagate viral spread. Targeted approaches that consider both sex and gender, as well as measures of intersectionality, are urgently needed in the response efforts against COVID-19.