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Background: Depression is a major cause of the global disease burden and globally affects 350-400 million persons making it the largest contributor to years lived with disability. Among of patients with chronic physical illnesses like tuberculosis, depression affects up to 25-33% of individuals. There are limited studies on the comorbidity of depressive illness and tuberculosis in the Ugandan setting. Our aim was to determine the prevalence and factors associated with depressive illness in patients with tuberculosis in Mulago Hospital, Uganda.Methods: This was a cross sectional study involving 308 consecutively sampled participants aged 18 years and above diagnosed with tuberculosis attending the tuberculosis clinic in Mulago Hospital, Uganda. Consecutive sampling was done for a sample size of 308 participants. Participants had the following instruments administered to them; the Socio-demographic questionnaire, the Mini Neuropsychiatric Interview (MINI) to diagnose depressive illness and the Patient Health Questionnaire- 9 to rate the severity of depression. Data was entered using Epi-Data. Descriptive, bivariate and multivariate analyses were done with the Statistical Package for Social Sciences (SPSS).Results: the prevalence of depressive illness was 23.7% (95% confidence interval 19.3-28.9). Depressive illness was independently associated with low education level (AOR = 0.39, 95%CI = 0.21-0.72, p = 0.003), being in the intensive phase of TB treatment (AOR = 2.34, 95%CI = (1.27-4.33), p = 0.007) and family history of depressive illness (AOR = 5.42, 95%CI = 2.02-14.54, p = 0.001). On the PHQ, 60.3% had moderate to severe depression.Conclusion: Depressive illnesses should be screened and managed among patients with TB.Recommendation: Depression should be routinely screened and managed among patients with Tuberculosis. [ABSTRACT FROM AUTHOR]