Aim: The research aimed to study the effect of interferon (IFN)-based drugs on the behavior of immunological parameters in calves during the specific prevention of associative infections. Materials and Methods: The object of research was 45 black motley cows and their calves from birth to 2 months of life. Serum and colostrum samples were screened for antibodies against Rotavirus, diarrhea, and coronavirus using serological methods. The testing was performed before vaccination, 40 days before calving, 20 days before calving, and before calving. Colostrum samples were taken during the first milk yield. Serum samples from calves were drawn before colostrum feeding as well as at 7, 14, and 21 days, and 1 and 2 months of age. To measure the level of immunoglobulins A, M, and G, additional serum samples were collected from calves at 25, 35, 65, and 75 days after birth. Results: Giving pregnant cows, an IFN-based drug at a dose of 1 ml/kg 48 h before vaccination results in the development and accumulation of antibodies to Rotavirus, coronavirus, and viral diarrhea (VD) in the colostrum, with a titer of 7.6±0.3 log , 5.8±0.34 log , and 4.4±0.18 log , respectively. It indicates an increase in the antigenic activity of the multivalent vaccine. Conclusion: IFN-based drugs enhance the protective effect of vaccination against associative infections in the newborn calves. They stimulate a rise in the titer of antibodies to Rotavirus, coronavirus, VD, and mucosal disease complex as well as an increase in immunoglobulins A, M, and G. 2 2 2