United States National Institutes of Health (NIH), Bethesda, MD, USA (R01AI097494 to JG). Additional support for this work was obtained through Federal funds from the Government of India’s (GOI’s) Department of Biotechnology (DBT; New Delhi), the Indian Council of Medical Research (ICMR; New Delhi, India), the United States NIH, National Institute of Allergy and Infectious Diseases (NIAID), Office of AIDS Research (OAR), and distributed in part by CRDF Global (Arlington, VA, USA) (USB1-31147- XX13 CRDF/NIH to AG), and the NIH-funded Johns Hopkins Baltimore- Washington-India Clinical Trials Unit for NIAID Networks (U01AI069465 to VM, NG, AG). RS was supported by NIH/National Institute of Child Health and Human Development grant R00HD089753. RL was supported by the BJGMC JHU HIV TB Program funded by the Fogarty International Center, Bethesda, MD, USA (NIH grant D43TW009574). ANG was supported by NIH Research Training Grant # D43 TW009340 funded by the NIH Fogarty International Center, the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health, the National Heart, Lung, and Blood Institute and the National Institute of Environmental Health Sciences (Bethesda, MD, USA). BBA was supported by Intramural research program from FIOCRUZ and from the National Institutes of Health (U01AI115940) and NIH/CRDF RePORT International Supplemental Funds. BBA is a senior investigator from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. KFF was supported by a postdoctoral fellowship from the CNPq, Brazil. MBA was supported by a PhD fellowship from the Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). JD is funded by European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant 677542), a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant 107613/Z/15/Z), and the Barts Charity (Grant MGU0343).Individuals with concurrent tuberculosis (TB) and Type 2 diabetes (DM) have a higher risk of adverse outcomes. To better understand potential immunological differences, we utilized a comprehensive panel to characterize pro-inflammatory and pro-resolving (i.e., mediators involved in the resolution of inflammation) lipid mediators in individuals with TB and TB-DM. A nested cross-sectional study of 40 individuals (20 newly diagnosed DM and 20 without DM) was conducted within a cohort of individuals with active drug-susceptible treatment-naïve pulmonary TB. Lipid mediators were quantified in serum samples through lipid mediator profiling. We conducted correlation-based analysis of these mediators. Overall, the arachidonic acid-derived leukotriene and prostaglandin families were the most abundant pro-inflammatory lipid mediators, while lipoxins and maresins families were the most abundant pro-resolving lipid mediators in individuals with TB and TB-DM. Individuals with TB-DM had increased correlations and connectivity with both pro-inflammatory and pro-resolving lipid mediators compared to those with TB alone. We identified the most abundant lipid mediator metabolomes in circulation among individuals with TB and TB-DM; in addition, our data shows a substantial number of significant correlations between both pro-inflammatory and pro-resolving lipid mediators in individuals with TB-DM, delineating a molecular balance that potentially defines this comorbidity.