There is a high prevalence of mental distress in people with TB associated with social, economic, and biological factors present from TB investigation through to post TB treatment. However, there is limited research to understand mental health experiences of people with TB and the current working practices to manage mental distress in people with TB by TB health workers. Additionally, little is known about the burden of mental distress in TB survivors in the sub-Saharan region. This mixed methods PhD aimed to critically reflect on the relationship between TB and mental health from TB investigation through to post TB treatment in Zambia. Study data is drawn from eight urban communities in Zambia. Qualitative methods explored: 1) drivers of mental distress as experienced by people with TB and perceived by TB health workers and stakeholders in Zambia; 2) how health workers manage mental distress in their clients with TB. In one community, quantitative analysis was used to compare the prevalence of mental distress in adult TB survivors to adults with no history of TB. Findings show that mental distress is prevalent among people with TB in this setting and ranged from mild to severe. Mental distress was driven by multi-layered and intersecting stresses, with the economic stress of poverty being the most powerful driver. TB health workers and stakeholders understood the economic drivers of distress in their clients but had a poor understanding of other causes of distress and no standard management practices for mental distress in their clients. Quantitative analysis indicates that TB survivors do not have a disproportionate burden of mental distress when compared to individuals without a history of TB in this setting. The thesis uses the findings to generate recommendations for comprehensive management of TB and mental distress using the WHO Innovative Care for Chronic Conditions framework.