Nutritional supplement of omega-3 fatty acids have been proposed to improve clinical outcomes in critically ill patients. While previous work have demonstrated that omega-3 supplementation in patients with sepsis is associated with reduced ICU and hospital length of stay, the financial impact of this intervention is unknown. Perform a cost analysis to evaluate the impact of omega-3 supplementation on ICU and hospital costs. We extracted data related to ICU and hospital length of stay from the individual studies reported in a recent systematic review. The Cochrane Collaboration tool was used to assess the risk of bias in these studies. Average daily ICU and hospital costs per patient were obtained from a cost study by Kahn etal. We estimated the ICU and hospital costs by multiplying the mean length of stay by the average daily cost per patient in ICU or Hospital. Adjustments for inflation were made according to the USD annual consumer price index. We calculated the difference between the direct variable cost of patients with omega-3 supplementation and patients without omega-3 supplementation. 95% confidence intervals were estimated using bootstrap re-sampling procedures with 1000 iterations. A total of 12 RCT involving 925 patients were included in this cost analysis. Septic patients supplemented with omega-3 had both lower mean ICU costs ($15,274 vs. $18,172) resulting in $2897 in ICU savings per patient and overall hospital costs ($17,088 vs. $19,778), resulting in $2690 in hospital savings per patient. Sensitivity analyses were conducted to investigate the impact of different study methods on the LOS. The results were still consistent with the overall findings. Patients with sepsis who received omega-3 supplementation had significantly shorter LOS in the ICU and hospital, and were associated with lower direct variable costs than control patients. The 12 RCTs used in this analysis had a high risk of bias. Large-scaled, high-quality, multi-centered RCTs on the effectiveness of this intervention is recommended to improve the quality of the existing evidence.