Previous studies demonstrated that immune dysregulation is an important cause of hepatitis B virus (HBV)‑mediated liver damage. Co‑stimulators including programmed cell death protein 1 (PD‑1) and inducible T cell co‑stimulator (ICOS) are involved in the pathogenesis of HBV. In the present study, the serum levels of soluble (s)PD‑1 and sICOS in patients with chronic HBV infections, were investigated, and the association between sPD‑1 and sICOS levels and liver injury degree was investigated. Serum sPD‑1 and sICOS levels were increased in the HBV‑patient group particularly in the HBV external core antigen positive group. In the immune clearance group, sPD‑1 and sICOS were increased compared with the tolerance group. Furthermore, the relative mRNA expression levels were also increased in patients with HBV. However there was no correlation between sPD‑1 and sICOS levels and HBV antibodies or PD‑1/ICOS mRNA copies. The altered sPD‑1 and sICOS serum levels in the different HBV groups may reflect the dysregulation of T cell activation, and may be associated with the HBV pathological process.