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Background About ten percent of European households across all socioeconomic groups are considered over-indebted due to ongoing difficulties meeting financial commitments and living expenses. Studies found an association between over-indebtedness and physical and mental health such as depression independent of standard socioeconomic status measures. However, antidepressant use in the over-indebted population has been understudied. In view of the substantial economic and social burden of mental illness in Europe, the aim of this study was to examine the association between over-indebtedness and antidepressant use in Germany to advance the understanding of socioeconomic inequalities in mental health. Methods We conducted a cross-sectional survey among clients of 70 debt advice agencies in North Rhine-Westphalia, Germany, in 2017 (OID), and merged data with the first wave of the German Health Interview and Examination Survey (DEGS1) representative of the general population. We used descriptive statistics and multiple logistic regression analysis to examine antidepressant use in the previous 7 days (OID: n = 699; DEGS1: n = 7115). Results Antidepressant use was more frequent in the over-indebted (12.3%) compared to the general population sample (5.0%). After adjustment for age, sex, education, employment, marital status and chronic disease, over-indebted respondents were more likely to use antidepressants than the general population sample (aOR 1.83; 95% CI 1.35-2.48). Conclusions Prevalence of antidepressant use was higher in the over-indebted compared to the general population. The association between over-indebtedness and antidepressant use cannot be fully explained by standard socioeconomic measures. Over-indebtedness reflects a relevant public health issue that needs to be addressed in health care, social policy and research. There is an urgent need to develop public health activities that specifically target those at risk of mental illness and over-indebtedness. Key messages Over-indebtedness is associated with antidepressant use. Public health interventions are needed to prevent adverse health effects of over-indebtedness and safeguard access to care according to need.