Each year, an estimated 1.5 and 11 million people died of tuberculosis and sepsis, respectively. Most cases occur in Low and Middle-Income Countries (LMICs). Gabon is listed in the top 30 tuberculosis/HIV high-burden countries. Studies performed for this thesis investigated the contributors to the burden of tuberculosis and sepsis in Gabon and suggested actions for improved control. Several research designs including a pragmatic clinical trial, systematic review and meta-analysis, cross-sectional, operational and qualitative studies have been combined to generate the outcomes reported in this thesis. The main findings were the following. There is a high prevalence of smoking in tuberculosis patients in Gabon (30%) and smoking is associated with diagnostic delay. Forty-six per cent (46%) of the tuberculosis patients had at least either dyslipidaemia, hypertension, diabetes, or obesity with a majority of newly-diagnosed hypertension and diabetes. One patient out of three with drug-resistant tuberculosis has never been treated for tuberculosis before, highlighting the urgent need to improve drug-resistant tuberculosis case-finding strategies at the community level for early diagnosis and treatment. Almost 64% of HIV-negative patients with tuberculosis sepsis died, and the diagnosis was obtained for 85% of them only post-mortem. Individual sepsis predicting scores such as qSOFA, SIRS, MEWS, and UVA, could not identify sepsis patients with accuracy but should be combined for better performance. Sepsis is a silent killer in many countries. Future research should be designed to provide the evidence needed to engage health policy stakeholders to consider sepsis as a global health priority.