Addressing the problem of septic arthritis, caused by Staphylococcus aureus, is a matter of high importance for poultry industry nowadays. We conducted research into effectiveness of antimicrobials of different groups used for treating experimental infection in two-week old chicks. In the first experiment we determined the effectiveness of florfenicol, ofloxacin and a compound drug, containing ciprofloxacin and apramycin (100 mg/g and 500 mg/g). Florfenicol and ofloxacin were administered at concentrations 300 mg/L, 200 mg/L, 100 mg/L and 50 mg/L of drinking water, while the compound drug – 200 mg/L, 100 mg/L, 50 mg/L and 25 mg/L (considering ciprofloxacin). In the second experiment we studied the effectiveness of tilmicosin, administered via drinking water at concentrations 500 mg/L, 250 mg/L, 125 mg/L and 62.5 mg/L simultaneously with the challenge. For the challenge of the chicks, we used pathogenic culture of S. aureus. S. aureus in suspension was injected intraperitoneally at a dose 3 x 108 cells in 0.5 mL of 0.9% saline (2 MсFarland standard) per chick. The observation period was 20 days during which we watched the chicks and registered their morbidity rate and mortality rate. We came to a conclusion that florfenicol was most effective when the treatment of the chicks began 24 hours prior to the challenge; in the same situation the compound drug, containing ciprofloxacin and apramycin, was slightly less effective. Under these conditions the survivability of the infected chicks was 84% to 96%. When the treatment with ofloxacin via drinking water began 24 hours prior to the challenge of the chicks, it was no use as morbidity rate and mortality rate were similar or even higher compared to the control group, irrespective of the dose. When the treatment with tilmicosin via drinking water began simultaneously with the challenge of the chicks, it was rather effective at medium and low doses of 125 mg/L and 62.5 mg/L. However, the mortality rate of the chicks was high and the morbidity rate reached 56%.