Obesity has been linked with low levels of ω-3 fatty acids. Generally, intervention studies have failed to establish benefits of supplementation with ω-3PUFA in reducing body weight or fat mass in humans. The aim of this study was to investigate whether supplementation with LCω-3PUFA alone, then consumed concomitantly with a very low energy diet (VLED), facilitated weight loss, improvements in blood lipids and positive changes to inflammatory mediators. This was a double blind randomised controlled trial with two parallel groups. For 4 weeks of prior supplementation, one group consumed 6 × 1 g capsules per day monounsaturated oil (placebo), the other group consumed 6 × 1 g capsules per day LCω-3PUFA (fish oil) each comprising 70 mg EPA and 270 mg DHA, while consuming their usual diet. Each group continued with their supplements for another 4 weeks while both groups followed a VLED regimen (n = 19 placebo, n = 20 fish oil). Fasting blood samples, anthropometric measurements and 3-day food diaries were collected at baseline, at 4 weeks and at 8 weeks. At 4 weeks levels of EPA and DHA increased two-fold in the fish oil group (P < 0.001), with no significant changes to anthropometric measurements for either group. At 8 weeks a significant 3-way interaction between time, group and gender was observed for percentage reduction in weight, F(1,35) = 5.55, P = 0.024, and BMI, F(1,35) = 5.3, P = 0.027 with a greater percentage decrease for females in FO compared to PB for weight (−7.21% vs. −5.82%) and BMI (−7.43% vs. −5.91%) respectively (P < 0.05 for both). It would appear that supplementation with LCω-3PUFA had a time dependent effect on weight loss in females.