Introduction Changes in the levels of DNA of hepatitis B virus (HBV) infection and the quantitative content of the surface antigen (HBsAg) in acute hepatitis B, as well as the concomitant co-injection of other hepatitis viruses have been insufficiently studied so far. Materials and Methods In 21 patients with acute HBV monoinfection and 27 patients with co-infection of HBV + HCV and/ or HDV three to four serum samples were withdrawn with interval of 6-10 days and the dynamics of HBV viral load and concentration of HBsAg was examined. Results Logarithm of the concentration of DNA HBV was established to decrease from 4.0 ± 0.65 to 3.0 ± 0.59, to 2.5 ± 0.47, to 1.9 ± 0.65 (IU /ml, M ± s), the half-life of DNA HBV was increased from 1.6 days at baseline to 4 days to the end of the study. The decline of the HBsA concentration proceeded much slower: from 38 to 23, 12, 3.8 pg/ml. Half-life period of HBsAg accounted of 8 days at the beginning and 5.7 days at the end of the study, however, in 11 patients there was observed rapid elimination of HBsAg and disappearance of HBV DNA. Conclusion The fact of co-infection with hepatitis C virus (HCV) had no significant effect on the dynamics of HBV DNA and HBsAg levels. In patients infected with Hepatitis D virus (HDV) HBV viral load was significantly lower, and the concentration of HBsAg, by contrast, is significantly higher than in acute monoinfection with HBV. Thus, in acute hepatitis B DNA elimination occurs much faster than the elimination of HBsAg. In addition, in co-infection HDV inhibits replication of HBV, but at the same time stimulates the expression of HBsAg. The obtained data should be considered in the interpretation of laboratory tests in patients with acute hepatitis B, both in the earlier period, and at follow-up.