Objectives: To determine the role of sIL-2R and sIL-2R/lymphocyte ratio as indicators of COVID-19 severity and predictors of clinical progression among children and adolescents. Patients and Methods: This observational cross-sectional study enrolled 76 pediatric patients [40 (52.6%) males and 36 (47.4%) females] with confirmed COVID-19. Patients were classified into two groups; mild to moderate and severe to critical according to WHO classification of severity and were assessed using COVID‑19 severity assessment score and COVID-19 severity index. Soluble IL-2R (sIL-2R) concentrations were measured using a commercial enzyme-linked immunosorbent assay and sIL-2R/lymphocyte ratio was calculated for each patient. Results: Receiver-operating characteristic (ROC) curve analysis showed that sIL-2R has a significantly higher discriminative power between patients in both groups (AUC=0.955) as compared to sIL-2R/lymphocyte ratio (AUC=0.711) (p < /em> value<0.0001). At an associated criterion of >140 ng/l, the sensitivity and specificity of sIL-2R were 81.4.% and 100%, respectively.  Soluble IL-2R also showed better performance in predicting the need for supplemental oxygen [threshold>140 ng/l, AUC=0.904 (0.814 to 0.960)], ICU admission [threshold>140 ng/l, AUC=0. 935 (0.854 to 0.979)], and mechanical ventilation [threshold>180 ng/l, AUC=0. 892 (0.799 to 0.951)]. Conclusion:  Soluble IL-2R can play a potential role as a feasible indicator of COVID-19 severity in children and adolescents, thus informing healthcare providers to direct care to patients who may require intensive or critical care.