Background: Type 1 diabetes Mellitus (T1DM) is a dynamic autoimmune disorder characterized by retrogressive insulin production as a consequence of autoimmune-mediated destruction of insulin producing pancreatic β-cells. This study aims at evaluating serum levels of soluble CD40 Ligand (sCD40L) as biomarker for early detection of complications associated with T1DM in children. Methods: A comparative cross-sectional study was conducted on 120 children with T1DM attending the Pediatric Diabetes Clinic of Beni-Suef University Hospital, in the period from April 2019 to January 2021. They were classified into 2 groups each with 60 patients, according to the presence or absence of microvascular diabetic complications. A group of 60 age and sex-matched healthy subjects were also included as a control group. Enrolled patients were subjected to detailed clinical evaluation, fundus examination, nerve conduction velocity, in addition to laboratory testing including fasting lipid profile, mean 2-hours postprandial blood glucose, Glycated hemoglobin (HbA1c), serum levels of sCD40L using enzyme linked immunosorbent assay (ELISA) and urinary albumin-to-creatinine ratio by an immuno-nephelometric method. Results: Patients' group comprised 68 males (56.7%) and 52 females (43.3%). The most common complication encountered in the studied patients with T1DM was micro albuminuria in 44 patients (73.33%), followed by peripheral neuropathy in 18 (30%) and retinopathy in two (3.33%). Serum sCD40L levels were significantly elevated in patients with complicated T1DM (6956±2025 pg/ml) compared to non-complicated group (547.7±125.4 pg/ml) and healthy controls (205.7±55.3 pg/ml) [p < 0.001]. A cut-off level of sCD40L more than 315 pg/mL could discriminate complicated from non-complicated cases with 96 % sensitivity and 90 % specificity, area under the curve 0.96 (p < 0.001). Serum sCD40L levels were positively correlated with HbA1c and urinary albumin excretion (p < 0.001). Conclusion: Serum sCD40L could be a helpful biomarker for monitoring microvascular complications of T1DM. Wider scale longitudinal studies might help to assess the value of sCD40L in following-up diabetic patients and predicting complications so that preventive measures can be timely taken.