In this study, we evaluated the expression of costimulatory molecule CD28 on circulating CD8+ T cells and the balance of CD8+CD28+ and CD8+CD28− T cells in patients with hepatitis B. Compared with healthy controls, high level of CD8+CD28− subpopulations and low CD28+/CD28− ratio in the CD8+ T cell population were observed in patients with hepatitis B. Similar variations in CD8+CD28− T cells proportions and CD8+CD28+/CD8+CD28− T cells ratio were also observed between HBeAg-positive group and HBeAg-negative group. Here, CD28 is linked to hepatitis B virus infection.