ABSTRACTBackgroundTransgender and non-binary people are disproportionately burdened by barriers to quality healthcare, mental health challenges, and economic hardship. This study examined the impact of the novel coronavirus disease (COVID-19) pandemic and subsequent control measures on gender-affirming care, mental health, and economic stability among transgender and non-binary people globally.MethodsWe collected global cross-sectional data from 964 transgender and non-binary adult users of the Hornet and Her apps from April to August 2020 to characterize changes in gender-affirming care, mental health, and economic stability as a result of the COVID-19 pandemic. We conducted Poisson regression models to assess if access to gender-affirming care and ability to live according to one’s gender were related to depressive symptoms, anxiety, and changes in suicidal ideation.ResultsIndividuals resided in 76 countries, including Turkey (27.4%,n=264/964) and Thailand (20.6%,n=205). A majority were non-binary (66.8%,n=644) or transfeminine (29.4%,n=283). Due to the COVID-19 pandemic, 55.0% (n=320/582) reported reduced access to gender- affirming resources, and 38.0% (n=327/860) reported reduced time lived according to their gender. About half screened positive for depression (50.4%,442/877) and anxiety (45.8%,n=392/856). One in six (17.0%,n=112/659) expected losses of health insurance, and 77.0% (n=724/940) expected income reductions. The prevalence of depressive symptoms, anxiety, and increased suicidal ideation were 1.63 (95% CI: 1.36-1.97), 1.61 (95% CI: 1.31-1.97), and 1.74 (95% CI: 1.07-2.82) times higher for individuals whose access to gender- affirming resources was reduced versus not.DiscussionThe COVID-19 pandemic has reduced access to gender-affirming resources and the ability of transgender and non-binary people to live according to their gender worldwide. These reductions may drive the increased depressive symptoms, anxiety, and suicidal ideation reported in this sample. To improve transgender and non-binary health globally, increased access to gender-affirming resources should be achieved through policies (e.g., digital prescriptions), flexible interventions (e.g., telehealth), and support for existing transgender health initiatives.