The study aims to evaluate the prevalence of depression and the severity of depressive symptoms among primary care patients, who are high utilizers (HU) of health care resources. A cross-sectional, two-stage design was applied to screen for depression using the Brief Psychiatric Health Questionnaire and the Diagnostic Expert System for Psychiatric Disorders. A total of 38 primary care physicians accredited to practice in Berlin and Potsdam in Germany participated in the study. A total of 1,775 patients participated, 507 were identified as HU, 182 (36 %) of these were depressed compared to 81 (11 %) of the typical utilizers (p < 0.001). The depression score was higher and acute suicidality was more prevalent in HU than in typical utilizers (p < 0.001). Our results suggest that HU represent a population with a high prevalence of depression in primary care and should be considered for routine depression screening.