Abstract Background Understanding how pandemics differentially impact on the socio-protective and psychological outcomes of males and females is important to develop more equitable public health policies. We assessed whether males and females differed on measures of major depression and generalized anxiety during the COVID-19 the pandemic, and if so, which sociodemographic, pandemic, and psychological variables may affect sex differences in depression and anxiety. Methods Participants were a nationally representative sample of Irish adults (N = 1,032) assessed between April 30th to May 19th, 2020, during Ireland’s first COVID-19 nationwide quarantine. Participants completed self-report measures of anxiety (GAD-7) and depression (PHQ-9), as well as 23 sociodemographic pandemic-related, and psychological variables. Sex differences on measures of depression and anxiety were assessed using binary logistic regression analysis and differences in sociodemographic, pandemic, and psychological variables assessed using chi-square tests of independence and independent samples t-tests. Results Females were significantly more likely than males to screen positive for major depressive disorder (30.6% vs. 20.7%; χ 2 (1) = 13.26, p
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