Imbalance of essential trace elements viz. Zinc, Selenium, Iron, Copper and Magnesium has been reported to influence disease course in HIV-1, HBV and HCV infections by altering immune status. A study was taken up to examine plasma levels of Th1 (IFN-γ and IL-2) and Th2 (IL-4 and IL-10) categories of cytokines and immune activation markers (TNF-α, TNFR I and TNFR II) in an asymptomatic group of HIV-1, HBV and HCV infected blood donors in relation to trace elements. Plasma levels of Zn, Se and Mg were depressed in all the three groups of blood donors (P < 0.001 for all). Levels of Cu and Fe were depressed in HIV-1 infection (P < 0.001 for both), but elevated in HBV and HCV infections (P < 0.015 and < 0.001 for Cu and < 0.001 for Fe in case of HBV and HCV infections respectively). IL-2 and IFN-γ were depressed in all the three groups of blood donors (P < 0.001). IL-4 and IL-10 levels were elevated in HBV and HCV infections (P < 0.001 for both). Immune activation markers were elevated in all the three groups of blood donors (P < 0.001 for all). HIV-1 infection showed positive correlations between Cu and IL-2, Zn and IFN-γ, and in HBV infection while positive correlations were found between Mg and TNFR I and TNFR II and Se with TNFR II. HCV infection showed a positive correlation between Se and IFN-γ (P < 0.001), Mg and IL-4 (P = 0.02), Fe and IL-10 (P < 0.01). The present study reveals possible relationship between trace element level alterations and alterations in cytokine and immune activation levels in HIV-1, HBV and HCV infection.