BACKGROUND: It is widely accepted that corticosteroids cause leukocytosis. Clinicians must decide whether a rise in white blood cell (WBC) count is due to steroids versus other processes like developing infection. OBJECTIVE: The objective of this study is to measure the increase in white blood cell count after corticosteroid administration in hospitalized patients without malignancy, infection, or immune dysfunction. METHODS: This is a retrospective cohort study from 2017 to 2018 in a single large healthcare system. We analyzed the trajectory of WBC count stratified by steroid dose. The study included nonsurgical patients admitted with at least two complete blood count measurements. Patients were excluded if they had immunosuppression, infection, malignancy, or steroid use within 2 weeks before admission. The main outcome was mean WBC count by day following corticosteroid administration. RESULTS: Our sample included 28,425 patients with at least two WBC measurements, 1608 (5.7%) of which received steroids. WBC response peaked at 48 h after steroid administration with a mean increase of 2.4 × 10 CONCLUSIONS: When interpreting WBC counts after initiating steroids, increases of up to 4.84 × 10