An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride–glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70–180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141–180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.