Background:  This is a case control study aimed to detect plasma level of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) cytokines in multidrug resistant tuberculosis (MDR-TB) co-infected with human immunodeficiency virus (HIV) patients and multidrug resistant tuberculosis (MDR-TB) monoinfected patients. Methods: This study determined the differences in plasma concentrations of pro-inflammatory (IL-2 and IFN-γ) cytokines in MDR-TB co-infected with HIV patients and MDR-TB monoinfected patients. Plasma levels of IL-2 and IFN-γ were measured in 130 participants (comprising 15 MDR-TB/HIV co-infected treatment naïve patients, 15 MDR-TB/HIV co-infected treatment experienced patients, 20 MDR-TB monoinfected treatment naïve patients, 20 MDR-TB monoinfected treatment experienced patients, 20 drug susceptible tuberculosis (DS-TB) co-infected with HIV treatment experienced patients and 40 apparently healthy control groups) using enzyme-linked immunosorbant assay (ELISA). Results: Shows that the mean plasma level of IL-2 (210.02 ± 59.27 pg/ml) measured in MDR-TB co-infected with HIV treatment-naïve patients (group 1a) was significantly (p < /em><0.026) lower compared to MDR-TB monoinfected treatment-naïve patients (244.20±108.07 pg/ml). Conversely the mean plasma levels of IFN-γ was significantly (p < /em><0.041) higher in MDR-TB/HIV co-infected treatment-naïve patients (group 1a) (8.31±3.56 pg/ml) compared to MDR-TB monoinfected treatment-naïve patients (group 2a) (6.89±2.14 pg/ml). Conclusion: Our study revealed significantly reduced plasma level of IL-2 in MDR-TB and HIV co-infected patients compared with MDR-TB monoinfected subjects, suggesting a more advanced immunodeficiency in co-infected patients.