Several studies investigated KIR3DS1 and KIR3DL1 in the context of various infections. However, none of the studies were performed on KIR3DS1/L1 in association with IFN-ɣ/IL-10 in TB, HIV-1, and their confections. We aimed to evaluate KIR3DS1/KIR3DL1 expression in association with IFNɣ/IL-10 in HIV-1 and TB mono-infections and HIV-1/TB confection and compared with uninfected controls using RTq PCR. We also performed correlation analysis between KIR3DS1, KIR3DL1, IFN-ɣ and IL-10 in the respective cohorts. The overall expression of KIR3DS1 was found to be downregulated in all groups, whereas in HIV-1 and HIV-1/TB, the frequency of KIR3DS1(+) expression was significantly (p \u3c 0.05) associated with undetected HIV-1 viral load. However, expression of KIR3DL1 was found to be significantly (p \u3c 0.05) upregulated in HIV-1 only. In addition, IFNɣ expression was significantly (p \u3c 0.05) decreased in TB, whereas in HIV-1/TB, IFNɣ expression was significantly (p \u3c 0.05) increased. In contrast, IL-10 expression was significantly (p \u3c 0.05) increased in HIV-1 and HIV-1/TB but not in TB. Also, we found significant positive correlation (p \u3c 0.05, r = 0.61) between KIR3DL1 and IFNɣ expression in TB and negative correlation (p \u3c 0.05, r = - 0.62) between KIR3DS1 and IL-10 in HIV-1/TB. In conclusion, we suggest that expression of KIR3DS1/L1 is associated with IFNɣ/IL-10 responses and it is involved in modulating disease severity in HIV-1 and TB infection