Background Brain disorders (neurological and mental disorders) are common and burdensome diseases. We examined occurrence, mortality, and economic burden of brain disorders in Denmark from 2015 to 2021. Methods We conducted a nationwide population-based cohort study using individual-level registry data. We computed the prevalence of any brain disorder and 25 individual brain disorders for each year from 2015 to 2021 and incidence for 2011-2015 and 2016-2021. We computed one-year hazard ratios (HRs) for all-cause mortality by comparing individuals with brain disorders to matched controls without and calculated attributable direct and indirect costs (i.e., economic burden) of brain disorders. Findings The prevalence of any brain disorder in Denmark was 1,893,318/5,705,540 = 33.2% in 2015, increasing to 2,059,852/5,856,666 = 35.2% in 2021. The most prevalent conditions were depression (793,419/5,856,666 = 13.5% in 2021), sleep disorders (788,209/5,856,666 = 13.5% in 2021), and headache (461,353/5,856,666 = 7.9% in 2021). The incidence rate of any brain disorder was 1792 and 1634 per 100,000 person-years in 2011-2015 and 2016-2021, respectively. The one-year HR of mortality for any brain disorder was 5.5 (95% confidence interval [CI]: 5.4; 5.6) for 2011-2015 and 5.3 (95% CI: 5.2; 5.3) for 2016-2021. The total attributable direct costs for individuals with any brain disorder were <euro> 7.5 billion in both 2015 and 2021. Total indirect costs increased from <euro> 17.7 billion in 2015 to <euro> 23.2 billion in 2021. Interpretation Brain disorders remain common, with a fi vefold higher one-year mortality compared to persons without brain disorders. While total direct costs were similar in 2015 and 2021, total indirect costs increased over Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).