A detailed phenotypic analysis of major and minor circulating lymphocyte subsets is described in potential blood donors with markers of hepatitis C virus (HCV), including non-viremic and viremic groups. Although there were no changes in the hematological profile of either group, increased the levels of pre-NK cells (CD3-CD16+CD56-) and a lower frequency of mature NK cells (CD3-CD16+CD56+) characterized innate immunity in the non-viremic group. Both non-viremic and viremic groups displayed significantly increased levels of CD56(Bright) NK cells. Furthermore, this subset was significantly elevated in the viremic subgroup with a low viral load. In addition, an increase in the NKT2 subset was observed only in this subgroup. An enhanced frequency of activated CD4+ T-cells (CD4+HLA-DR+) was a characteristic feature of the non-viremic group, whereas elevated CD19+ B-cells and CD19+CD86+ cell populations were the major phenotypic features of the viremic group, particularly in individuals with a low viral load. Although CD4+CD25High T-cells were significantly elevated in both the viremic and non-viremic groups, it was particularly evident in the viremic low viral load subgroup. A parallel increase in CD4+CD25High T-cells, pre-NK, and activated CD4+ T-cells was observed in the non-viremic group, whereas a parallel increase in CD4+CD25High T-cells and CD19+ B-cells was characteristic of the low viral load subgroup. These findings suggest that CD56Bright NK cells, together with pre-NK cells and activated CD4+ T-cells in combination with CD4+CD25High T-cells, might play an important role in controlling viremia. Elevated CD56(Bright) NK cells, B-cell responses and a T-regulated immunological profile appeared to be associated with a low viral load