BACKGROUND: Alterante-day fasting regimens have been suggested as a possible approach for calorie restriction and weight loss. The aim was to compare the effect of a 6-week weight loss regimen based on the Mediterranean diet versus the Mediterranean diet with 5-day semi-fast, in achieving weight loss in overweight or obese people. METHOD: Randomized, controlled, prospective, semi-clinical trial of 41 participantes, aged 30 to 65 years, with overweight type II (BMI >27) or obesity (BMI >30). Subjects were distributed by randomization in group 1 (Mediterranean diet + semifast) and group 2 (standard hypocaloric Mediterranean diet). Anthropometric measurements were taken and eating habits of the participants were recorded. RESULTS: No statistically significant differences were found when comparing anthropometric measurements between groups. Similar changes were observed between the two groups. However, when analysing anthropometric measurements inter-group, statistically significant differences (p<0.05) were obtained within each group. CONCLUSION: The low calorie Mediterranean diet and the low calorie Mediterranean diet + semi-fast diet used in this study appear to be equally as effective in decreasing body weight, fat mass, visceral fat mass and waist circumference. However, semi-fast regimens may be superior to daily restriction regimens in facilitating weight loss. These findings add to the growing body of evidence showing that altenate-day fasting regimens may be implemented as another viable option for weight loss in overweight and obese populations.