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The coronavirus disease 2019 (COVID‐19) pandemic has created unprecedented challenges worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes COVID‐19 and has a complex interaction with the immune system, including growing evidence of sex‐specific differences in the immune response. Sex‐disaggregated analyses of epidemiological data indicate that males experience more severe symptoms and suffer higher mortality from COVID‐19 than females. Many behavioural risk factors and biological factors may contribute to the different immune response. This review examines the immune response to SARS‐CoV‐2 infection in the context of sex, with emphasis on potential biological mechanisms explaining differences in clinical outcomes. Understanding sex differences in the pathophysiology of SARS‐CoV‐2 infection will help promote the development of specific strategies to …