Background: Thyroid dysfunction, termed “euthyroid sick syndrome", was described in critically ill patients, but data in pediatric sepsis is limited. Objective: Our objective was to evaluate prevalence and prognostic value of this syndrome among children with sepsis. Patients and Methods: Prospective observational study including 81 children admitted into Pediatric Intensive Care Unit (PICU) with sepsis. Patients were classified on admission into “sepsis", “severe sepsis", and “septic shock" groups. Pediatric Index of Mortality2 (PIM2) was calculated. Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were measured upon PICU admission. Results: Hormonal abnormalities were detected in 57 (70.4%) patients. 52 patients had FT3 deficiency; 7 had FT4 deficiency; 23 had TSH deficiency; and two had TSH elevation. The predominant pattern was isolated FT3 deficiency (32.1%) then combined FT3 and TSH deficiency (23.4%). Mean FT4 was lower among “septic shock" compared with “sepsis" and “severe sepsis" groups (p=0.001). TSH was lower among severe sepsis than sepsis (p=0.033). FT3, FT4, and TSH were lower among patients needing vasoactive medications (p=0.046, 0.037, and 0.022 respectively). TSH was lower among patients requiring mechanical ventilation (p=0.003). FT3, FT4, and TSH inversely correlated with vasoactive infusion days. TSH inversely correlated with mechanical ventilation duration and PIM2. No specific hormone was associated with mortality, but TSH predicted “unfavorable course" i.e., the composite outcome of mortality or presence of ≥ one illness severity indicator (area under receiver operating characteristic curve=0.70). Conclusion: Euthyroid sick syndromeis common in pediatric sepsis. TSH and FT4 are particularly associated with illness severity.