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Prevalences for mental disorders within minor refugees are comparatively high and heterogeneous. To reduce heterogeneity and identify high-risk subgroups, we compared unaccompanied refugee minors (URM) to accompanied refugee minors (ARM) regarding depressive symptoms and mental distress. Furthermore, we examined associative factors of mental distress in URM on a broad scale. We conducted a survey with a cross-sectional design in four German University hospitals. The sample consisted of n = 172 URM and n = 52 ARM aged 14–21. Depressive symptoms were assessed via the Patient Health Questionnaire (PHQ-9). Mental distress was assessed by the Refugee Health Screener (RHS-15). Mann–Whitney test was used to examine differences between URM and ARM. Associated factors of mental distress were evaluated via a stepwise multiple regression analysis. URM showed significantly higher mean scores for PHQ-9 (p <.001) and RHS-15 (p <.001) compared to ARM indicating medium effect sizes. Furthermore, URM were significantly more likely to surpass the cut-off for depression (61.6% vs. 30.8%) and overall mental distress (81.4% vs. 53.8%) compared to ARM. The factors Number of stressful life events (SLE), Female gender, and Fear of deportation were found to be associated with an increased mental distress in URM, whereas Weekly contact to a family member, School attendance, and German language skills were accompanied with lower distress scores. All six factors accounted for 32% of the variance of mental distress in URM (p <.001). Within minor refugees, URM are a highly vulnerable subgroup, which should receive particular attention and more targeted measures by health authorities. Our results indicate that these measures should comprise a rapid promotion of family contact, school attendance, language acquisition, and the fast processing of asylum applications. However, the cross-sectional design limits the interpretability of the results. [ABSTRACT FROM AUTHOR]