Background: Epstein-Barr virus related acute pharyngotonsillitis is common in children and adolescents, and is generally managed successfully with positive outcomes by both ENT specialists and the pediatricians. However, a variety of acute, life-threating complications can occur, including upper airway obstruction and infectious or dysimmune sequelae. Methods: This paper describes our recent experience with four pediatric patients presenting with severe ENT manifestations of infectious mononucleosis (IM) that led to life-threating complications, all managed over the past three years at our tertiary pediatric hospital. Results: We report four cases (two boys and two girls) aged 5 to 16 years, hospitalized with complicated EBV-related pharyngotonsillitis. Presentations included respiratory distress (cases 1 and 2), fatal hemophagocytic lymphoistiocitytosis (case 3), and a retropharyngeal abscess (case 4). Conclusions: The prognosis of IM in the pediatric population is generally favourable. However, acute life-threating complications may arise. In such cases, timely and coordinated multidisciplinary management involving ENT specialists, pediatricians, and anesthesiologists is critical.