Adequate adrenocortical function is essential to survive critical illness. The goal of this study was to determine whether eosinophilia could serve as a useful and early marker of adrenal insufficiency in critically ill patients with severe septic shock. During a 1-year period, we prospectively studied 294 ICU patients.16 patients (5.4% of ICU admissions) with eosinophilia more than 3% of the white blood cell count and septic shock unresponsive to adequate fluid and vasopressor therapy, were included. A high dose (250 mcg i.v) corticotropin stimulation test was performed. Eosinophilia (>3%) was diagnosed in 16 patients with vasopressor-unresponsive septic shock. Eosinophilia was present 1.9±0.9d (range 8-96h) before the onset of septic shock. 11/16 patients failed to respond to corticotropin stimulation test above the critical level of 9 mcg/dL rise and 2/16 had baseline cortisol concentration <10 mcg/dL. Baseline cortisol level, maximal cortisol increase post-corticotropin administration and Eosinophils count (%) were higher in survivors (p≤0.05). A hydrocortisone infusion (300mg/d) treatment resulted in haemodynamic improvement in 12 of 16 patients (75%). The 28-day mortality (following the onset of septic shock) was 43.7%. Relative eosinophilia may be considered as a useful and early bioassay for adrenocortical function assessment in critically ill patients with septic shock and assumed adrenocortical depression.