Introduction: Sepsis is a leading cause of mortality in critically ill patients on the intensive care unit (ITU). Death from sepsis in the ITU is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with omega-3 (fish oil) has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial in reducing morbidity from organ dysfunction. Method: A randomised control trial investigating the effects of parenteral omega-3 (OmegavenTM), given early in the course of sepsis, was carried out in a single institution. Consecutive patients diagnosed with sepsis were entered into the study. Patients were randomised to receive either parenteral fish oil and standard medical care or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the SOFA score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C-reactive protein (CRP), days free of organ dysfunction/failure and fatty acid (FA) analysis. Results: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral fish oil were associated with a significant reduction in new organ dysfunction (delta-SOFA 2.2±2.2 vs. 1.0±1.5, p=0.005 and maximum-SOFA 10.1±4.2 vs. 8.1±3.2, p=0.041) and mean CRP (186.7±78 vs. 141.5±62.6, p=0.019). There was no significant reduction in the length of ITU and total hospital stay between cohorts. Patients treated with fish oil in the strata of less severe sepsis had a significant reduction in mortality (p=0.042). Conclusion: The treatment of critically ill septic patients with parenteral fish oil is safe. N-3 FAs are rapidly taken up by circulating white cells. It is associated with a significant reduction in organ dysfunction and CRP. It may be associated with a reduction in mortality in patients with less severe sepsis. A multi-centre trial is justified as a result of this trial.