The Indonesian government has identified six pillars of Health Transformation as a means of improving community self-reliance, including the management of Non-Communicable Diseases (NCDs) such as diabetes. However, during the COVID-19 pandemic, diabetes cases can result in death if the patient is infected with COVID-19, and the disease can also lead to increased fatigue. The purpose of this study is to identify factors associated with fatigue in patients with Type 2 Diabetes Mellitus during the COVID-19 Pandemic. This descriptive research employed a cross-sectional design. It used Chi-Square and logistic regression analyses to identify the dominant factor associated with fatigue. The study population consisted of patients with type 2 diabetes who visited the Integrated Development Post (Posbindu) in four working areas of the Public Health Center in Palembang City during the pandemic. We used purposive sampling to select the respondents, and the number of respondents was 293. Our findings indicate that more than 50% of people with diabetes experience severe fatigue during the pandemic. Low education and depression were identified as the primary factors contributing to fatigue in people with diabetes, while individuals with diabetes who work and have an abnormal body mass index (BMI) were identified as protective factors against fatigue after controlling for education and depression variables. Our study suggests that the management of diabetics during the COVID-19 pandemic requires comprehensive interventions beyond medical interventions. Stress management and education interventions are also needed to help patients maintain their quality of life during the pandemic.