The role of spexin (SPX) in energy metabolism, endocrinal homeostasis, and vasculopathy is emerging. However, scarce data are available about its role in childhood obesity and obesity-related vasculopathy. Hence, we aimed to assess the level of SPX in obese and normal-weight children, and to correlate it with aortic distensibility (AD) and aortic stiffness index (ASI). Forty obese children were compared to 40 matched normal-weighed children. Weight, height, and body mass index (BMI) z score and mean blood pressure (Bl-Pr) percentile on three different occasions were obtained. SPX, fasting triglycerides, cholesterol, low-density (LDL), high-density lipoproteins (HDL), and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR). Internal aortic diameter was measured with calculation of AD, strain (AS), and ASI. Children with obesity had significantly lower SPX (P = 0.004), HDL (P < 0.001), and AD (P < 0.001) and higher systolic Bl-Pr (P < 0.001), diastolic Bl-Pr (P < 0.001), LDL (P = 0.011), HOMA-IR (P < 0.001), and ASI (P < 0.001). Significant negative correlation was found between SPX and BMI z score (r = -0.646, P < 0.001), systolic Bl-Pr (r = -0.641, P < 0.001), diastolic Bl-Pr (r = -0.427, P < 0.001), HOMA-IR (r = -0.349, P = 0.028), and ASI (r = -0.389, P = 0.013), while significant positive correlation was found between SPX and AS (P < 0.001, r = 0.633) and AD (P < 0.001, r = 0.612). However, no significant correlation was found between SPX and age (r = -0.01, P = 0.953), TG (r = 0.048, P = 0.767), total cholesterol (r = -0.023, P = 0.887), LDL (r = -0.299, P = 0.061), and HDL (r = 0.193, P = 0.232). Children with obesity had significantly lower SPX than controls. SPX was correlated with BMI, Bl-Pr, HOMA-IR, and vasculopathy in children with obesity independent of their age and lipid profile. Further studies should explore the pathomechanism of SPX and its potential role in the management of obesity and obesity-related cardiometabolic risk.