Background Bacteriophages can be successfully applied to treat infections caused by antibiotic-resistant bacteria. Until now no attempts have been undertaken to treat infections in immunosuppressed patients with phages. In this work we investigated the prophylactic efficacy of specific bacteriophages in CBA mice treated with cyclophosphamide (CP) and infected with Staphylococcus aureus. Results High numbers of bacterial colony-forming units in the organs as well as elevated tumor necrosis factor and interleukin-6 serum concentrations in CP-treated and S. aureus-infected mice were significantly lowered upon application of phages. The phages markedly increased the percentage of circulating neutrophils and immature cells from the myelocytic and lymphocytic lineages in CP-treated, S. aureus-infected mice as well as of myelocytes and immature neutrophils in the bone marrow. In addition, phages stimulated in such mice generation of specific agglutinins against S. aureus. Conclusion Application of specific phages to immunosuppressed mice prior to infection with S. aureus proved very effective, suggesting a potential benefit of phage therapy in immunocompromised patients experiencing bacterial infections.