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Background: Septic shock, a condition caused by a dysregulated host response to systemic infection, may cause life-threatening organ dysfunction. During sepsis, concentrations of corticosteroid-binding globulin (CBG) in the serum progressively decrease. Therefore, the CBG nadir could play a role in septic shock-related organ failure and mortality. Non-thyroidal illness is a non-thyroidal illness syndrome that refers to changes in thyroid function tests in the inpatients of intensive care units having critical illnesses because of transient changes in the hypothalamicpituitary-thyroid axis that can be explained as a homeostatic mechanism to conserve energy. Aim of the Work: to evaluate the relation of serum CBG and thyroid hormone levels to organ dysfunction and mortality rates in pediatric patients with septic shock. Patients and Methods: We conducted a prospective observational study on 91 pediatric patients with proved sepsis during the period from May 2023 to November 2023 at pediatric intensive care unit (PICU) of Ain shams university hospitals, serum CBG level was measured after at least 6 hours of initiation of inotropes. Thyroid hormones were measured for all patients. The primary outcome was overall ICU mortality and morbidity. Secondary outcomes were 28 and 90-day-mortality, need for mechanical ventilation, renal replacement therapy, need for cardiac inotropic support including the dose and duration of cardiac support infusion, and the need for shock dose steroids. Results: Ninety-one patients were included and subdivided into two groups: survivors (42.9%) and non-survivors (57.1%). A cutoff value of 222.3 mg/dl was calculated for serum CBG levels using the Receiver Operating Characteristic curve (ROC) and Interactive Dot Diagram to differentiate between survivors and non-survivors creating a sensitivity and specificity of 98.08 and 3 1.58 % respectively. Primary outcome: The overall ICU mortality rate due to septic shock was significantly higher in patients with serum CBG levels less than 222.3 mg/dl, p-value=0.000. Secondary outcomes: 28-day mortality rates were higher in patients with CBG levels < 222.3 mg/dl, p-value = 0.00. Also, the need for mechanical ventilation was higher in patients with serum CBG levels < 222.3 mg/dl. There was no significant difference between patients with serum CBG levels <222.3 mg/dl and patients with serum CBG levels > 222.3 mg/dl regarding the need for noradrenaline and dopamine use However, patients with serum CBG <222.3 mg/dl needed higher noradrenaline and dopamine doses when used and a higher need for adrenaline and milrinone use, with longer infusion duration. The prevalence of non-thyroidal illness was 46.1%. Patients with non-thyroidal illness (changes in thyroid hormones levels during critical illness without clinical manifestations) had higher SOFA scores. There was no significant difference between the patients with normal thyroid profiles and non-thyroidal illness patients regarding mortality, dose of cardiac inotropic support, or organ dysfunction. Conclusion:Septic shock patients with CBG < 222.3 mg/dl had a higher need for ventilatory support, vasopressors, and 8.4-fold higher ICU mortality. Non-thyroidal illness is common in septic shock patients with higher SOFA scores but is not associated with a higher mortality rate. [ABSTRACT FROM AUTHOR]