- Background Glucocorticosteroids (GCS) are known to cause the hematologic effect of leukocytosis and neutrophilia. Leukocytosis is a key parameter in establishing the diagnosis of sepsis and in the estimation of its severity. Objective To quantify the effect of chronic or acute GCS treatment on the level of leukocytosis in patients with acute infectious process. Methods We conducted a retrospective cohort study of patients with an acute infection hospitalized in tertiary medical center between the years 2003–2014. Patients were classified into three categories: chronic GCS treatment, acute GCS treatment, no GCS treatment. The primary outcome was the maximal WBC count within the first 24 h from admission. Results We identified 5468 patients with acute infection: 333 of them with chronic GCS treatment, 213 with acute GCS treatment and 4922 with no GCS treatment. The overall maximal leukocytes count was higher in GCS therapy groups: 15.4 ± 8.3 × 109/L for the acute GCS treatment, 14.9 ± 7.4 × 109/L for chronic GCS treatment and 12.9 ± 6.4 × 109/L for the no GCS group (P < 0.001). Conclusion In patients with acute infections chronically treated with GCS, an increase in the WBC is at average of 5 × 109/L. These data must be taken into consideration while using the level of leukocytosis as a parameter in the diagnosis of the infectious process.