The study was aimed at determining the protective value of the coupled application of immunomodulation and vaccination in the prophylaxis of mycoplasmal pneumonia of swine (MPS). It was conducted on a pig farm, on 28 piglets with body weights of 7-8 kg in the peri-weaning period, divided into four groups of 7 animals each. In the experiment, the following were used: Bioimmuno preparation (Institute of Inland Fisheries, Olsztyn) elaborated based on methisoprinol and Saccharomyces cerevisiae, to be administered with feed, as well as an inactivated vaccine against MPS - Respisure One (Pfizer). The first two groups of piglets were administered Bioimmuno with a feed mixture at a dose of 1 kg/50 kg feed for 48 hours prior to the immunization of one of the groups with Respisure One on day 28 of life. The third group of piglets was only vaccinated, whereas the fourth group served as control. Clinical observations were conducted that covered the monitoring of side reactions (local and constitutional), an evaluation of the incidence and character of symptoms manifested by the respiratory system and other health status disorders as well as the determination of the number and percentage of medical interventions and death cases of animals. Animal husbandry examinations and post-slaughter analyses involved the determination of the mean body weight at slaughter, mean daily body weight gains, mean daily feed utilization, and mean feed conversion ratio per 1 kg b.w. gain and an index of quantitative lesions in the lungs. The study did not demonstrate any local side reactions at an injection site of the Respisure One vaccine nor any constitutional side reactions linked with the administration of either preparation. In turn, the clinical and animal husbandry examinations showed a positive effect of administering the Bioimmuno immunomodulator on the effectiveness of immunization against MPS with the Respisure One vaccine and on the improvement of the health status of pigs, which was manifested by a reduced incidence of infections in the piglets with respiratory symptoms, increased b.w. gains, improved feed utilization and shortened fattening period. Due to the diminished intensification of respiratory symptoms and pathological lesions in lungs and the improved fattening indices, the coupled administration of the Bioimmuno and Respisure One biopreparations to piglets may constitute an important element of MPS prophylaxis in pig herds.