Background Thrombosis and embolism are possible complications in coronavirus disease 2019 (COVID)‐19‐positive pediatric patients. Although the risk is lesser in children than it is in adults, it does exist during acute infection and multi‐inflammatory syndrome in children. Biomarkers such as d ‐dimer, prothrombin time, and fibrinogen degradation products are ineffective at detecting disease severity. Homocysteine (Hcy) is a prothrombotic factor that has been reported to be higher in adult COVID‐19 patients, leading to speculation that it could be used as a biomarker for disease severity. Purpose To detect the correlation between serum total homocysteine (tHcy) level and the severity of COVID‐19 in pediatrics. Methods A cross‐sectional study was conducted on 40 children with COVID‐19 and 40 healthy control subjects. Serum tHcy was measured by enzyme‐linked immunosorbent assay and correlated with the clinical, laboratory, and radiological parameters of the patients. Results The median serum tHcy level in COVID‐19 patients was 27.5 (interquartile range [IQR]: 23–31.75) μmol/L, while that in the controls was 1.8 (IQR: 1.6–1.875) μmol/L. There was a statistically significant increase in the tHcy level in cases compared to controls ( p < 0.001). There was a statistically significant positive correlation between serum tHcy and d ‐dimer, ferritin, alanine transaminase, aspartate transaminase, blood urea nitrogen, and a highly significant positive correlation between tHcy and COVID‐19 reporting and data system score, pediatric intensive care unit admission, and the disease severity classification. Conclusion Hcy could be a biomarker of importance in predicting the severity of COVID‐19 in pediatrics.