Introduction: Informed consent was obtained to publish this description. A 65-year-old man is presented in another local hospital with head trauma 4 weeks ago. During its initial management the patient developed a urinary sepsis associated with a generalized rash; this was the cause for the change of the prophylactic phenytoin by valproic acid. Due to the stability of the clinical condition, he was transferred to the medical ward where symptoms were persistent and his condition deteriorated. He needs a referral for critical care but there was no availability of beds by what is transferred to our institution. After researching, a history of seizures was not identified. The patient had no significant medical history, drug allergies, or alcohol use. It refers to a history of 1-week of fever associated with a rash on his chest, face and extremities, altered mental status and drowsiness. On initial examination, the patient was found to have a temperature of 38.5 grades, a heart rate of 110 beats/minute and blood pressure of 90/60 with support of norephineprine 0.2 mcg/kg/min, a respiratory rate of 24 breaths/minute, and an oxygen saturation of 100% with oxygen administered by face mask. The patient was malnourished, and was treated with a second antibiotic treatment with meropenem. There was an eruption near erythrodermatic in the face, upper and lower extremities and trunk, without involvement of the oral mucosa, palms, or soles. There was a profound generalized edema. His abdomen was soft and relaxed without guarding, or hepatosplenomegaly. Any focal deficits were identified in the neurological examination. At this point, the differential diagnosis included urinary sepsis with multiple organ dysfunction or drug-induced hypersensitivity. The patient´s condition continued to deteriorate over the following 24 hours. Impaired renal function associated with oliguria. Serum creatinine reached a high of 1.86 mg/dL. He requires increasing doses of vasopressors agents and developed respiratory failure requiring mechanical ventilation. He also developed the deterioration of liver function with a transaminases increase 5 times above normal level. The leukocyte count increased to a peak leukocytosis of 13.100 with an eosinophilia of 35%. There was a significant discussion about the possibility of recurrence of infection due to the severity of the clinical condition of the patient. However, no evidence of infection had been identified. The team made a diagnosis of DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) due to the continuous use of valproic acid. The valproic acid and meropenem was suspended and methylprednisolone 500 mg/day for 3 days was initiated followed by prednisolone 60 mg/day. Skin biopsies revealed superficial dermis with edema, discrete spongiosis and superficial perivascular lymphocytic inflammatory infiltrate with eosinophils in the interstitium. During the next 48 hours, the patient made a clear and fast recovery. The vasopressors was quickly suspended. The dynamic ventilatory improved achieving extubation in the sixth day of intensive care unit; the kidney and the liver also improved, but the improvement of skin lesions was slower. The patient was transferred to the room 10 days after his admission to the ICU. He was discharged 4 days later. Steroids were removed completely without complication within three months. No sequels or recurrence were reported. °