Staphylococcus aureus is the causative agent of a wide range of infections, including severe systemic diseases, which is often multidrug resistant. Given the growing overall antibiotic resistance, a promising approach to treating staphylococcal infections is administration of bacteriophages, especially in combination with antibiotics. This study aimed to evaluate the synergistic effect of linezolid and bacteriophage vB_SauM-515A1 in combating a systemic infection in BALB/c mice. Using 36 animals, we established the optimal way of administration and the infecting dose of the microorganism (5 × 10⁸ CFU/mouse intravenously), and identified the threshold concentrations of antimicrobial agents for monotherapy. The evaluation was based on the revealed contamination of internal organs (kidneys, spleen) and blood. To learn the etiotropic effect of linezolid (10 mg/kg animal weight) combined with the phage (2 × 10⁷ PFU/mouse), we worked with a control group and a test group, 12 mice in each; 2, 8, 18, and 24 hours after infection, the former received the drug only, the latter — the investigated combination. Combined therapy had a more pronounced effect, decreasing the bacterial load in the kidneys by two to three orders of magnitude compared with monotherapy on the first day of treatment. Thus, the combined use of linezolid and bacteriophages is promising for the treatment of infections caused by S. aureus, and may increase the effectiveness of treatment and reduce the risk of side effects of high-dose antibiotics.