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Purpose: The COVID-19 pandemic has had a profound impact on mental health worldwide, with depression and sleep problems among the most common issues experienced by many individuals. Depression can lead to sleep problems, which can increase the risk of developing depressive symptoms. However, it is unclear which United States (US) sub-population was most affected by depression and sleep problems during the pandemic., Methods: We conducted a secondary analysis using self-reported data from the 2021 National Health Interview Survey (NHIS), focusing on adults aged 18 years and above (n=29,763). We utilized self-reported responses to questions about prescription medication and frequency of depressive feelings to determine participants' depression status. Appropriate weights were applied to account for the sampling design of the surveys. Our analysis involved descriptive statistics and chi-squared tests to compare sociodemographic, clinical, behavioral, and sleep-related characteristics between US adults with and without depression. Additionally, logistic regression was used to examine the associations between sleep duration, sleep quality and depression., Results: The overall prevalence of depression in our sample was 44.4%. It were higher in certain demographic groups, including younger adults (18-39 years, 47.7%), non-Hispanic whites (47.9%), females (50.1%), those at the lower income bracket (52.2%), those with no college or degree (48.7%) uninsured individuals (45.2%), and those reporting poor general health (71.9%). Individuals with depression had a 12% increased odds of experiencing short sleep (aOR: 1.12, 95% CI:1.04-1.20, p<0.001), 34% increased odds of experiencing long sleep (aOR: 1.34, 95% CI: 1.20-1.50, p < 0.001) and more than 2.5 fold increased odds of reporting poor sleep quality (aOR:2.57, 95% CI: 2.40-2.78; p<0.0001). In the multivariate analysis, all variables (sex, race/ethnicity, education, health insurance coverage, marital status, general health status and use of sleep medications, smoking and alcohol use status) were significantly predictors of poor sleep quality, with the exceptions of age and family income., Conclusion: The findings emphasize the need to address sleep health in treating depression, especially during times of public health crises., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chery et al.)