The diagnosis of the DRESS syndrome should be highly suspected in patients with fever, skin rash, liver involvement, hypereosinophilia and lymphadenopathy that develop during the use of a culprit drug. We report the first case of DRESS syndrome associated with cefotaxime and clindamycin exposure in a 6-year-old boy. Early recognition of the signs of the DRESS syndrome and immediate cessation of the suspected drug are the most important steps for an appropriate management of the syndrome. Pediatricians should be careful about this potential complication associated with these commonly prescribed antibiotics in pediatric practice.