Aims We aimed to determine the contribution of quantitative HBsAg in differentiating chronic infections from chronic hepatitis in HBeAg negative patients with HBV DNA 2000-20,000 IU/ml. Material and methods A total of 79 untreated HBeAg negative patients were included. Patients were divided into 3 groups based on HBV DNA levels: group 1 (HBV DNA <= 2000 IU/ml), group 2 (HBV DNA: 2000-20,000 IU/ml) and group 3 (HBV DNA > 20,000 IU/ml). We collected serum from all patients for quantitative HBsAg analysis. We compared serum quantitative HBsAg levels with biochemical parameters, HBV DNA and liver biopsy results. Results In this study 46 patients were female and the mean age was 42 years. Serum quantitative HBsAg levels were found to be significantly lower in chronic infections compared with chronic hepatitis. There was a positive correlation between quantitative HBsAg and HBV DNA, ALT (alanine aminotransferase), HAI score (histological activity index), fibrosis score and disease stage. The cut-off level of quantitative HBsAg was determined as 4425 IU/ml to differentiate chronic infection from chronic hepatitis. With the test specificity of 95%, we found quantitative HBsAg cut-off values 1026 IU/ml and 20,346 IU/ml for the diagnosis of chronic infection and chronic hepatitis, respectively. Conclusion Our study suggests that the quantitative HBsAg <= 1000 IU/ml limit value might be used for the diagnosis of chronic infection not only in HBV DNA <= 2000 IU/ml but also in patients with HBV DNA between 2000-20,000 IU/ml. In addition, antiviral treatment could be considered in patients with quantitative HBsAg > 20,000 IU/ml and HBV DNA > 2000 IU/ml without further examinations such as liver biopsy.