The objectives of this review were to determine whether the long-chain omega-3 fatty acids eicosapentaenoic acid and/or docosahexaenoic acid dose-dependently reduce fasting serum triglycerides (TG) and, if so, to create a mathematical model that may be used to predict potential percent reductions in fasting serum TG levels at the recommended intakes of 200–500 mg/day. The assessment included 15 randomized controlled trials that met pre-defined inclusion and exclusion criteria. Across these 15 studies, the dose-response was modeled using a first-order elimination curve. The response variable was defined as percent change from baseline in fasting serum TG, adjusted for the placebo effect. A weighting factor equal to the product of each study's sample size and quality score was used. Using the equation of the dose-response curve, predicted reductions in fasting serum TG levels at the recommended long-chain omega-3 fatty acid intakes of 200–500 mg/day are 3.1 to 7.2%.