BACKGROUND: Obesity is associated with elevated levels of inflammation and metabolic abnormalities, with increased risk of developing insulin resistance, type 2 diabetes, stroke and CVD. Nutrients that can assist in weight loss may also reduce the risk of obesity related co-morbidities. AIM: The aim of this study was to investigate whether LCn-3PUFA, combined with a reduced energy diet, facilitated weight loss and improvements in blood lipids and inflammatory mediators. DESIGN: A double blind randomised controlled trial with two parallel groups. Both groups followed a low energy diet for 12 weeks, one group consumed 6 × 1 g capsules/d monounsaturated oil (Placebo) (n = 18), the other 6 × 1 g capsules/d LCn-3PUFA (fish oil) (n = 17). Fasting blood samples, anthropometric measurements and 3-day food diaries were collected at baseline and post intervention. RESULTS: There was a two-fold increase in plasma levels of EPA and DHA in the fish oil group (p < 0.001). There were no significant difference within and between the placebo and the fish oil groups for weight reduction (3.37% and 4.35% respectively), fat mass reduction (8.95% and 9.76% respectively), or changes in inflammatory biomarkers and blood lipids apart from triglycerides, reduced by 27% in fish oil group (p < 0.05). For fish oil group there were significant correlations between leptin and weight loss (p = 0.01) and leptin and EPA and DHA (p < 0.05 for both). CONCLUSION: Dietary LCn-3PUFA supplementation during a weight loss program does not appear to assist weight loss. Poor dietary compliance may be a contributing factor in accurate assessment of the role of these fatty acids in weight loss.