BACKGROUND: Depression is an important potential comorbidity in persons with tuberculosis (TB), yet data in many settings are scarce. OBJECTIVE: To estimate the prevalence and risk factors of depression in persons with multidrug-resistant tuberculosis (MDR-TB) in Myanmar. METHODS: A cross-sectional survey among MDR-TB participants at Aung San MDR-TB treatment centre in Yangon during routine clinic follow-up visits. Patients Health Questionnaire-9 (PHQ-9) in the local language was used to screen for depression and structured questionnaires conducted. Univariable and multivariable logistic regression models were performed to identify associations. RESULTS: Three-hundred and twenty-nine participants were enrolled between 19th December 2019 and 31st January 2020; 33% (111/329) in the intensive treatment phase. The prevalence of depressive symptoms (PHQ-9 ≥ 10) was (34/329) 10.33%. Multivariable analysis indicated financial hardship as a result of MDR-TB symptoms/treatment (aOR = 2.63, 95%CI: 1.12-6.67), suffering ≥1 respiratory symptoms (aOR = 6.72, 95%CI: 2.41-18.76), high education level (aOR = 4.26, 95%CI: 1.70-10.70), reported diabetes (aOR = 3.05, 95%CI: 1.16-7.99) as associated with depressive symptoms, with weak evidence of an association in females (aOR = 2.09, 95%CI: 0.94-4.65). CONCLUSION: Depressive symptoms are more common in those with comorbidities/TB symptoms. Further research is required to determine the effects of interventions to support persons with depressive symptoms identified using simple, standardised validated tools like PHQ-9.