Most studies have focused on mother-to-child transmission and postpartum hepatitis flare. We intended to evaluate the expression profile of pregenomic RNA (pgRNA) and its factors in chronic HBV infection (CHB) patients during pregnancy and postpartum. 134 pregnant and 100 postpartum CHB patients were enrolled, and the levels of serum pgRNA were quantified. There were significant differences in clinical characteristics between the pregnant and postpartum CHB patients, but there was no significant difference in pgRNA levels between the two groups. When the levels of HBV DNA and HBV antigen were low, the corresponding pgRNA detection rate decreased. pgRNA was positively correlated with DNA and HBV antigen in the pregnancy and postpartum CHB patients. In the pregnant group, antiviral treatment was an independent risk factor for pgRNA levels; in the postpartum period, HBeAg levels and antiviral treatment were independent risk factors for pgRNA levels. Considering that patients under antiviral treatment are often accompanied by a high DNA load or positive HBeAg, it is the DNA level and HBeAg that affect the level of pgRNA essentially. pgRNA levels show different profiles in pregnancy and postpartum, which is of great significance for the diagnosis and management of these particular groups.