Background/aim: This study aimed to assess expression changes of serum sPD-1 levels in HBeAg-positive chronic hepatitis B patients with entecavir treatment and explore the correlation with the curative effect. Materials and methods: A total of 220 HBeAg-positive CHB patients and 207 healthy individuals were included. sPD-1 levels and virological and biochemical responses were assessed at baseline and at 12, 24, and 48 weeks in CHB patients a er antiviral therapy. Results: sPD-1 levels in HBeAg-positive CHB patients before treatment were signi cantly lower than those of healthy controls. After entecavir treatment, sPD-1 levels increased gradually over time. At 48 weeks a er entecavir treatment, sPD-1 amounts in the HBeAg seroconversion group were signi cantly higher than the values of the HBeAg-negative and HBeAg-positive groups. sPD-1 levels in patients with alanine aminotransferase (ALT) returning to normal were signi cantly higher than in those with ALT not returning to normal. sPD-1 levels in treated patients with no HBV-DNA were signi cantly higher than in those with HBV-DNA remaining positive. sPD-1 was negatively correlated with ALT and HBV-DNA at 12, 24, and 48 weeks a er entecavir treatment. Conclusion: sPD-1 may play a certain role in chronic hepatitis B and has a close relationship with the curative effect of entecavir.