Résumé : Introduction: Contrasting with the lymphopenia classically reported after administration of glucocorticoids, a lymphocytosis has been sometimes observed in patients after glucocorticoid administration. We here determine prospectively the timing and magnitude of methylprednisolone (mPDN)-induced lymphocytosis and study the effects of concomitant propranolol administration on lymphocyte count (Ly). Methods: Ly was measured before and 24 to 72 hours after initiating mPDN treatment in 20 patients with immune-mediated inflammatory disorders (IMID). After one week, patients with increased Ly were divided in two groups receiving, in addition to mPDN, either propranolol or a placebo; Ly was determined 4 days later. Lymphocyte subpopulations and mPDN plasma levels were determined in subsets of the patients. Values are expressed as median with 25%–75% interquartile range. Results: A 73.4% (37–305) increase of Ly was observed in 18/20 patients as soon as 48 (48–72) hours after initiating mPDN (32 mg; 16–32). Lymphocytosis (Ly ≥ 4000/μL) was observed in 7 patients and hyperlymphocytosis (Ly ≥ 5000/μL) in 4 of them. The increase in Ly was noted both for B and T cells. Median mPDN plasma levels (n = 13) were 97.4 ng/mL (IQR 67–489) and 3.2 (IQR 2.1–5.1) respectively 8 hours and 24 hours after oral mPDN administration. No significant change in Ly was shown under propranolol (p = 0.570). Conclusion: A morning lymphocytosis observed during mPDN treatment occurs in the very first days of mPDN administration. Our results do not support the hypothesis of an increased adrenergic tone responsible for this phenomenon. Identifying this unexpected etiology of lymphocytosis could mitigate the need for unnecessary supplementary investigations in clinical practice.