We have established a cohort of 64 Natural Viral Suppressors (NVS) (similar to Elite Controllers/Elite Suppressors), 30 of which have chronic hepatitis C virus (HCV). We investigated T-cell phenotypic changes in association with HCV infection. NVS without HCV and normal controls had similar T-cell phenotypes. However, NVS with HCV had lower naive cell proportions (CD4 and CD8) compared with NVS without HCV (P = 0.0008 and P = 0.02) or normal controls (P = 0.0163 and P = 0.017). These results and previously reported data suggest that HCV coinfection increases immune activation and T-cell disturbances. Any associated T-cell functional changes or potential clinical consequences need further study.