Background: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Methods: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4{}^{+} T cells including circulating Tfh cells, CD8{}^{+} T cells, and TCR iV\alpha7.2{}^{+} MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-\alpha, IFN-\gamma) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. Results: The activation marker CD69 was significantly increased in CD4{}^{\text{+hi}} T cells, while CD8{}^{+} MAIT cells producing IFN-\gamma were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-\alpha{}^{+}CD4{}^{\text{+lo}} T cells, CD69{}^{+}CD8{}^{+} T cells, CD69{}^{+}CD4{}^{+} MAIT cells, PD-1{}^{+}CD4{}^{\text{+hi}} T cells, PD-1{}^{+}CD8{}^{+} T cells, and Ki67{}^{+}CD4{}^{+} MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-\alpha levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Conclusion: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.