Background <p>Morbid obesity is a multifactorial disease that impacts cardiovascular system. Endothelial progenitor cells (EPCs), which play a critical role in endothelial repair and angiogenesis, are dysregulated in obesity. The comparative effects of bariatric surgery and dietary intervention on EPCs and oxidative stress remain incompletely understood. This study aimed to evaluate changes in EPC concentrations, oxidative stress levels, antioxidant activity, lipid profile, and insulin sensitivity in women with morbid obesity undergoing Roux-en-Y gastric bypass (RYGB) versus diet restriction.</p> Methods <p>Seventy-two female subjects with obesity (BMI &gt; 30&#xa0;kg/m²) were randomly divided into two groups (<i>n</i> = 36 each): one underwent RYGB surgery, and the other followed a restricted diet. EPCs were measured by flow cytometry, while oxidative stress markers and antioxidant enzymes were determined using an enzymatic colorimetric method. Insulin levels were measured by the ELISA technique, and the spectrophotometric method was used for the determination of fasting blood glucose and lipid profile.</p> Results <p>Both interventions significantly reduced BMI, lipid levels, and oxidative stress, in addition to improving antioxidant capacity and insulin sensitivity. However, the RYGB procedure induced greater improvements across all metabolic and oxidative parameters. EPC declined significantly post-intervention, more markedly in the RYGB group (50%) than the diet group (42.85%). This decrease likely reflects a reduction in endothelial injury and hypoxic signaling.</p> Conclusion <p>RYGB surgery is more effective than diet restriction in reducing oxidative stress, improving antioxidant defense, and restoring EPCs homeostasis. These benefits may reflect reduced vascular stress and improved endothelial function, supporting RYGB surgery as a potent metabolic intervention for morbid obesity.</p>