Objective: To evaluate the alteration of plasma levels of signal peptide-CUB-EGF domain-containing protein (SCUBE)-1 as a marker of endothelial dysfunction and vascular injury in gestational diabetes mellitus (GDM) in comparison to healthy pregnant controls. Methods: A prospective study conducted at an antenatal outpatient clinic of a University hospital. Fifty pregnancies with GDM and thirty healthy pregnancies as controls were enrolled in the study. Results: There was no statistically significant difference between the groups in terms of age, gravidity, weight and BMI from pre-pregnancy until delivery, total weight gain, fetal weight and other hematological and biochemical parameters. SCUBE-1 levels were significantly higher in GDM patients (p = .007). Conclusions: Hyperglycemia predisposes to endothelial injury and vascular remodeling at GDM, and therefore, SCUBE-1 could be a predictor of vascular injury during pregnancy. Our study is the first to illustrate increased SCUBE-1 levels in GDM as a marker of placental endothelial dysfunction.