Background:Coexistence of mental health problems on diabetes mellitus can result in poor management of the illness, poor adherence to treatment, and low quality of life. Therefore, it is highly crucial to assess these problems; thus we carried out this study with the aim of determining the prevalence of depression and identifying related factors among diabetic patients at city of Mekelle, North Ethiopia.Methods:Hospital-based cross-sectional study was employed among 264 diabetic patients, and participants were selected through systematic random sampling technique. We used local language versions of Beck Depression Inventory-II, Beck Anxiety Inventory, and Morisky 8 Item Medication Adherence Scale to assess the levels of depression, anxiety, and medication adherence, respectively. Socio-demographic and clinical factors were also assessed. We accomplish data entry, cleaning, and analysis through Statistical Package for Social Sciences window 20; also the level of significance was determined using adjusted odds ratio (OR).Results:The prevalence of depression among diabetic patients is 17% (95% confidence interval [CI]: [12.9%, 21.6%]). In addition, 28% and 18.2% has low medication adherence and comorbid anxiety, respectively. We identify anxiety disorder (AOR = 10.52, 95% CI: [4.56, 24.28]), poor medication adherence (AOR = 4.38, 95%CI: [1.98, 9.64]), and coexistence of other physical illness (AOR = 3.04, 95% CI: [1.11, 8.34]) as risk factors for depression.Conclusions:Depression is a common mental health problem among diabetic patients which is related to poor treatment adherence coexistence of other physical illness and anxiety disorder. This emphasizes to formulate a mechanism for early detection and appropriate intervention.