BackgroundDepression in TB patients carries a heightened risk of treatment failure and a lower quality of life. However, no study to date has documented depression prevalence among TB patients in Afghanistan. ObjectivesWe aimed to assess depression prevalence in TB patients in Southern Afghanistan. MethodsBetween February 2023 and May 2024, a sample of 1,003 TB patients aged 18 years and above were randomly sampled in Southern Afghanistan. The questionnaire gathered patients’ sociodemographic information, clinical characteristics, social support level, and the PHQ-9 (Patient Health Questionnaire). We fitted a binary logistic regression model to identify correlates of depression symptoms among TB patients. ResultsOut of 1,003 patients, 69.6% (95% CI: 66.6%-72.4) had depression symptoms. We found that patients with no formal education [AOR = 3.18, 95%CI (2.35–4.30)], those with severe disease [1.84 (1.30–2.59)], patients with medical comorbidity [1.88 (1.29–2.74)], and those with low social support [1.69 (1.22–2.33)] were more likely to have depression symptoms. ConclusionTB patients in Afghanistan have high levels of depressive symptoms. Therefore, this study advocates for dedicated mental health screening and counseling services for TB patients in Afghanistan.