Background: Viral load has been used to diagnose and monitor patients who are being treated for chronic hepatitis B (CHB). The Diagnosis methods are molecular-based and expensive. Quantitation of hepatitis B surface antigen (HBsAg) by automated chemiluminescent micro-particle immunoassay has been proposed to be a surrogate marker.Quantitating HBV DNA levels molecularly is expensive; thus, a cheaper laboratory test as a surrogate diagnostic marker might simplify our management.Objectives: We determined whether quantitative HBsAg levels correlate with HBV DNA levels in CHB.Patients and Methods: In this cross-sectional study, all CHB patients who were referred by a gastroenterologist to undergo quantitative HBV DNA assay in a qualified laboratory in Mashhad, Iran in 2009 were enrolled, and blood samples was obtained. Patients who were positive for antibodies to HCV and HDV were excluded. HBV DNA was measured by real-time polymerase chain reaction, and serum HBsAg was quantified byelectrochemiluminescence assay (Roche Diagnostic).Results: Of 97 patients, 70 were male (72%) and 27 were female (28%); the mean age was 39 ± 11 years. Eighty-seven percent wasHBeAg-negative. By Mann-Whitney test, HBSAg titer differed significantly between HBeAg-positive and -negative patients (P=0.001), as did HBV DNA levels (P=0.009). By Spearman test, there was no significant correlation between HBsAg and HBV DNA levels (P=0.606 and r=0.53).Conclusions: HBeAg-negative patients have higher levels of HBsAg and lower levels of HBV DNA. By electrochemiluminescence assay, HBsAg has no significant correlation with HBV DNA levels in CHB with predominant genotype D and HBeAg negativity in Iran.