Background. The aim of nutritional therapy ill cancer patients is to prevent weight loss and to improve functional capacity and quality of lite. Clinical Studies however, have continued to demonstrate that a reduction in body Weight loss is difficult to achieve in cancer cachexia. Several studies have shown that supplementation with eicosapentaenoic acid (EPA), on omega-3 fatty acid, has anticachectic effects in adult cancer patients. This study evaluated the clinical effects of a protein and energy dense EPA containing nutritional supplement ill a group of pediatric cancer patients receiving active chemotherapy treatment. Methods. The study was a prospective, randomized, single ( enter, open-label design. Fifty-two patients diagnosed with pediatric malignant disease and receiving intensive chemotherapy were included. Thirty-three patients receiving a nutritional Supplement containing EPA in addition to their regular food intake. Nineteen control patients did not receive supplementation. Patients were examined and their data (body Weight, body mass index, and weight percentile) were recorded regularly once a month for 3 months. A subgroup of patients was evaluated for 6 months. Results. At 3 months, there were significantly fewer patients in the treatment group as compared to controls that showed losses in body weight (P = 0.001), BMI (P = 0.002), and a negative deviation in weight percentile (P = 0.021). In addition, remission rate was significantly (P = 0.036) higher in the treatment group as compared to controls. Conclusions. This Study demonstrates a decrease in cancer-induced weight loss in pediatric patients fed a protein and energy dense nutrition Supplement containing EPA. Pediatr Blood Cancer 2009;52:571-574. (C) 2008 Wiley-Liss, Inc.