Study Objectives: Sleep disordered breathing (SDB) has been associated with increased inflammatory responses. Changes in the level of pro-inflammatory leukotrienes (LTs) may initiate or exacerbate pediatric SDB and may play a major role in end-organ morbidity. The objective of the study was to investigate the relationship of LT productions with severity of SDB, obesity, and adenotonsillar hypertrophy in children. Design/Interventions: Prospective, observational study that included standard questionnaires, physical examinations, overnight polysomnography (PSG), and urinary leukotriene E-4 (LTE4) assay. Setting: Sleep Center and Laboratory of Nutriology. Patients or Participants: 282 children with SDB and 94 healthy control subjects were recruited. Measurements and Results: Urinary LTE4 levels were elevated in children with SDB compared to the controls, and LTE4 productions emerged disease severity- and obesity-dependent increases. In stepwise multiple regression analysis, the independent predictors of the apnea-hypopnea index (AHI) included LTE4 level and adenotonsillar-size sum score (P < 0.001 respectively; adjusted R-2 = 0.318). A positive relationship between LTE4 urinary level and adenotonsillar-size sum scores was present in the underweight/normal weight SDB subjects (r = 0.276; P < 0.001), but not in the overweight/obese children (P > 0.05). Conclusions: Systemic inflammation mediated by LTs participates in the pathophysiological mechanisms of SDB in children. The magnitude of inflammation as reflected by urinary LTE4 is significantly related to the severity of SDB and obesity. However, a correlation between LTE4 concentration and adenotonsillar size in present only among nonobese children.