Abstract: Objective To study the correlation between serum HBV covalently closed circular DNA (ccc DNA) and current serum levels of AST, ALT, TBIL, HBeAg and HBV DNA in chronic hepatitis-B (CHB) patients. Methods Fifty-eight CHB patients admitted to Chinese PLA 309 Hospital from May 2009 to May 2012 were enrolled in this study. Their serum levels of HBeAg were measured with Roche C6000 electrochemiluminescence method, their serum levels of ALT, AST and TBIL were measured with Hitachi Hi7600 automatic biochemical analyzer, and their serum levels of HBV DNA and HBV cccDNA were measured by RT-PCR. Results The serum HBV cccDNA was closely correlated with the serum HBV DNA (r=0.880, P=0.000). The proportion of positive HBV cccDNA was significantly higher in HBeAg-positive patients than in HBeAg-negative patients (67.6% vs 37.5%, χ²=5.170, P=0.023). The serum HBV cccDNA was positively correlated with the severity of liver inflammation (χ²=4.819, P=0.028). Conclusion Quantitative detection of serum HBV cccDNA is a reliable index for the assessment of HBV replication and liver cell damage.