Weight loss (WL) diets lower heart disease risk factors, and protein-pacing calorie restriction (P-CR, more than 25% of calories from protein) is one of the most efficacious interventions to treat obesity. During fat loss polychlorinated biphenyls (PCBs) are released into the blood stream and can disrupt metabolic and endocrine function in humans, having an adverse effect on health. The primary aim of this study was to compare changes in serum PCBs and oxidative stress biomarkers between obese men and women following a short-term P-CR diet. Participants, who were all overweight or obese, followed a P-CR WL diet which included 1 day per week of intermittent fasting (less than 330-430 kcal/day) for 12 weeks, a protein drink and a protein bar were provided. After the initial 12 weeks, participants self-selected to either continue with the P-CR diet or follow an approved “heart healthy” diet (HH) for one year. Laboratory tests were done at baseline, week 12 and at the end of the study (64 weeks). Weight loss was observed in the initial 12 weeks and was accompanied with an increase in PCBs, with no difference between men and women. Oxidative stress markers were decreased and total antioxidant capacity (TAC) was increased. After 64 weeks changes in circulating PCBs were higher in those who lost more body weight and fat. PCBs decreased more in the HH group than the P-CR group, which was associated with an increase in weight in the HH group. No significant difference was found in terms of oxidative stress and antioxidant status between P-CR and HH group. The authors concluded that a P-CR diet is an effective dietary intervention to induce weight loss, as well as mobilise stored PCBs and improve redox status.