The aim of this prospective, observational study was to determine the accuracy of a real-time continuous glucose monitoring system (CGMS) in children with septic shock. Subjects and Methods: Children aged 30 days to 18 years admitted to the Pediatric Intensive Care Unit with septic shock were included. A real-time CGMS sensor was used to obtain interstitial glucose readings. CGMS readings were compared statistically with simultaneous laboratory blood glucose (BG). Results: Nineteen children were included, and 235 pairs of BG-CGMS readings were obtained. BG and CGMS had a correlation coefficient of 0.61 (P < 0.001) and a median relative absolute difference of 17.29%. On Clarke's error grid analysis, 222 ( 94.5%) readings were in the clinically acceptable zones (A and B). When BG was < 70, 70-180, and > 180 mg/dL, 44%, 100%, and 76.9% readings were in zones A and B, respectively (P < 0.001). The accuracy of CGMS was not affected by the presence of edema, acidosis, vasopressors, steroids, or renal replacement therapy. On receiver operating characteristics curve analysis, a CGMS reading < 97 mg/dL predicted hypoglycemia (sensitivity 85.2%, specificity 75%, area under the curve [AUC] =0.85). A reading > 141 mg/dL predicted hyperglycemia (sensitivity 84.6%, specificity 89.6%, AUC =0.87). Conclusion: CGMS provides a fairly, accurate estimate of BG in children with septic shock. It is unaffected by a variety of clinical variables. The accuracy over extremes of blood sugar may be a concern. We recommend larger studies to evaluate its use for the early detection of hypoglycemia and hyperglycemia.