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Background Diabetes-related distress lowers the motivation for self-care, often leading to lowered physical and emotional well-being, poor diabetes control, poor medication adherence and increased mortality among individuals with diabetes.Objective To assess factors associated with diabetes-related distress among people living with type 2 diabetes in Southeast Ethiopia.Design Institution-based cross-sectional study was conducted.Setting Six diabetic follow-up care units at public hospitals in Southeast Ethiopia.Participants All adult people living with type 2 diabetes from the diabetic follow-up clinic.The main outcome measures Diabetes Distress Scale-17 questionnaire was used to assess diabetes-related distress.Results Out of the total 871 study participants intended, 856 participated in the study with a response rate of 98.3%. The findings showed that about 53.9% (95% CI 50.4% to 57.2%) of the patients have diabetes-related distress. Physical activity (adjusted OR, AOR 2.22; 95% CI 1.36 to 3.63), social support (AOR 4.41; 95% CI 1.62 to 12.03), glycaemic control (AOR 2.36; 95% CI 1.35 to 4.12) and other comorbidities (AOR 3.94; 95% CI 2.01 to 7.73) were factors that significantly associated with diabetes-related distress at p<0.05.Conclusion This study demonstrated that more than half of the participants had diabetes-related distress. Therefore, the identified factors of diabetes-related distress need to be a concern for health institutions and clinicians in the management of people living with type 2 diabetes.