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Objective To evaluate the humanistic and economic burden of migraine with versus without comorbid depression in European countries, South Korea and Brazil.Methods This observational, cross-sectional study included respondents of the 2020 (South Korea and Brazil) and 2022 (France, Germany, Italy, Spain, United Kingdom) National Health and Wellness Survey who self-reported physician-diagnosed migraine for ≥12 months, had active migraine for ≤12 months, and ≥4 headache days in the preceding month, with or without depression. Outcomes included migraine-related disability (MIDAS), health-related quality of life (EQ-5D Index) and total costs.Results Among respondents in Europe (N=1073), Brazil (N=331) and South Korea (N=219), 35.7%, 32.9% and 36.5% had depression, respectively. Across all regions, respondents with versus without depression had a greater number of migraines in the past 30 days (mean: Europe, 7.2 vs 5.0; p<0.001; Brazil, 9.2 vs 6.5; p<0.001; South Korea, 8.7 vs 6.1, p=0.004); and greater disability (MIDAS score ≥20: Europe, 60.8% vs 30.1%; Brazil, 65.1% vs 35.6%; South Korea, 48.8% vs. 20.9%; all p<0.001). Respondents with versus without depression had lower EQ-5D Index scores (all p<0.001); and higher direct and indirect costs (all p<0.001).Conclusion People with migraine and active depression experience higher humanistic and economic burden compared with those without depression.mark.fredericks@tevauk.com