UNLABELLED: Coronavirus disease 2019 (COVID-19) and COVID-19-related multisystem inflammatory syndrome in children (MIS-C) is known to be a life-threatening health problem worldwide. The study investigates the potential relationship between asymmetric dimethylarginine (ADMA) levels and disease severity in such conditions. We conducted an observational, prospective study between July 2021 and January 2022. The study enrolled 98 patients diagnosed with COVID-19, 21 patients diagnosed with MIS-C, and 42 healthy individuals who served as a control group. The COVID-19 patients were further categorized into three subgroups based on their level of care: outpatients, those requiring hospitalization, and those requiring intensive care. The MIS-C patients formed a distinct fourth group. COVID-19 outpatients had a median ADMA level of 8097.0 ng/L (interquartile range: 6436.06-10840.0 ng/L), while those requiring hospitalization had a higher level of 13,195.60 ng/L (11,472.4-15,862.2 ng/L). Patients in intensive care exhibited the highest median ADMA level at 19,361.4 ng/L (15,596.65-23,367.9 ng/L). MIS-C patients also had elevated ADMA levels, with a median of 15,735.50 ng/L (13,486.6-20,532.5 ng/L). Receiver operating characteristic (ROC) curve analysis revealed that an ADMA level of 6135.15 ng/L could distinguish between patients and controls with 95% sensitivity, 100% specificity, 100% positive predictive value, and 87.5% negative predictive value. CONCLUSIONS: In conclusion, our study is the first to investigate ADMA levels in children with COVID-19 and MIS-C. We found that ADMA levels were significantly elevated in children with COVID-19 requiring intensive care and those with MIS-C, suggesting a potential role for ADMA as a biomarker of endothelial dysfunction in these populations. WHAT IS KNOWN: • Endothelial dysfunction is a determinant of poor prognosis in various cardiovascular diseases and plays a critical role in the pathogenesis of COVID-19 and MIS-C. • Asymmetric dimethylarginine (ADMA) is a well-known biomarker of endothelial dysfunction. Elevated levels of ADMA adversely affect vascular endothelial function by reducing nitric oxide production. WHAT IS NEW: • It is the first to show that elevated ADMA levels in children with COVID-19 and MIS-C are associated with disease severity. • ADMA has been identified as a potential biomarker that can be used to assess the prognosis of COVID-19 and MIS-C in children and to predict the severity of the disease.