Background/Aim: Leptin plays an important role in energy metabolism. The primary objective of the study was to investigate whether baseline leptin levels predict weight loss during a dietary intervention in overweight and obese individuals. Methods: A total of 324 individuals (138 men and 186 women, aged 20–40 years, BMI 27.5–32.5) were recruited in Iceland, Ireland and Spain. The intervention lasted for 8 consecutive weeks, and subjects were instructed to follow a diet, energy restricted by 30%. Anthropometric variables were assessed before and after the intervention. Leptin concentration was measured at baseline and corrected for fat mass. Linear models were used to find out which variables predicted weight loss. Results: At end point, significant weight loss was observed (5.16 ± 3.06 kg, p < 0.001). High baseline leptin concentrations were a significant negative predictor of weight loss in men (p = 0.028), with a predicted difference of 1.8 kg between the lowest and highest leptin quartile. Conclusion: Our study underlines the importance of leptin in energy metabolism. Plasma leptin concentrations at baseline are a predictor of weight loss in overweight men after an 8-week dietary intervention. The same effect was not observed in overweight women, which suggests that the role of leptin in the regulation of weight is gender specific.