Introduction Tuberculosis (TB) infections and latent Mycobacterium tuberculosis (MTB) infection (LTBi) remain prevalent globally. Type 2 diabetes mellitus (DM) worsens TB outcomes but the immune mechanisms that cause this are not yet clear. We investigated a role of suppressor of cytokine signaling molecules (SOCS1 and SOC3) in regulating host cytokine responses in the diabetic host infected with MTB. Materials and Methods We studied peripheral blood cells from health endemic controls (EC), LTBi cases, diabetics with and without LTBi and TB patients. Mycobacterial antigen-stimulated cytokine secretion was determined using the Th1/Th2 11 plex cytokine assay. Antigen-induced gene expression of IFNγ, TNFα, IL6 and SOCS3 was determined by reverse-transcription PCR. Results Purified protein derivative (PPD) antigen stimulation induced higher levels of, IL-6, IL-2, TNFα and GM-CSF levels in DM-LTB as compared with EC and LTB cases. IL-13 levels were raised in DM-LTB cases as compared with DM cases. PPD-induced IFNγ and IL-6 transcripts were raised in DM-LTBi as compared with EC. TNFα mRNA levels were raised in DM-LTBi as compared with LTBi. SOCS3 mRNA levels were reduced in DM-LTBi as compared with LTBi. SOCS3 transcripts were higher in LTBi as compared with EC and TB groups. Discussion We found co-occurrence of LTBi with DM to be associated with an increased release of proinflammatory IL-6, IL-2 and TNF-α but reduced SOCS3 mRNA levels. SOCS3 protects against MTB infection therefore, reduced levels in DM-LTB may be contribute to progression from LTBi to active TB in individuals infected with MTB.