AIM: To investigate the effect of omega-3 fatty acid parenteral supplementation postoperatively on clinical outcomes and immunomodulation in colorectal cancer patients.METHODS: Forty-two patients undergoing radical colorectal cancer resection with an indication for total parenteral nutrition postoperatively were enrolled in this prospective, double-blind, randomized, controlled study.Patients received total parenteral nutrition supplemented with either soybean oil (LCT; Intralipid(R), Fresenius-Kabi,SO group, n = 21) or a combination of omega-3 fish oil and soybean oil (LCT:fish oil = 5:1, fish oil; Omegaven(R),Fresenius-Kabi, FO group, n = 21), up to a total of 1.2 g lipid/kg per day for 7 d postoperatively. A same volume calorie and nitrogen was administrated.Routine blood test, biochemistry, systemic levels ofIL-6 and TNF-α, percentage of CD3+, CD4+, and CD8+lymphocytes were evaluated preoperatively and on postoperative d 1 and 8. Patient outcome was evaluated considering mortality during the hospital stay, length ofpostoperative hospital stay, and occurrence of infectiouscomplications.RESULTS: Both lipid regimens were well tolerated.No differences between the two groups were noticedin demographics, baseline blood test, biochemistry,serum levels of IL-6 and TNF-o~, percentage of CD4+,CD8+ lymphocytes, and ratios of CD4+/CD8+. Comparedwith those on postoperative d 1, serum IL-6 levels onpostoperative d 8 were significantly depressed in the FO group than in the reference group (-44.43 ± 30.53 vs-8.39 ± 69.08, P = 0.039). Simultaneously, the ratios of CD4+/CD+ were significantly increased in the FO group (0.92± 0.62 vs 0.25± 1.22, P = 0.035). In addition,depression of serum TNF-α levels (-0.82 ± 2.71 vs0.27 ± 1.67, P = 0.125) and elevation of CD3+ and CD4+lymphocyte percentage (12.85 ±11.61 vs 3.84 ± 19.62,P = 0.081, 17.80 ±10.86 vs 9.66 ± 17.55, P = 0.084,respectively) were higher in the FO group than in the reference group. Patients in the FO group trended to ne eda shorter postoperative hospital stay (17.45 4. 4.80 dvs 19.62 4. 5.59 d, P = 0.19). No statistically significantdifference was found when stratified to mortality and occurrence of infectious complications.CONCLUSION: Postoperative supplementation of omega-3 fatty acids may have a favorable effect on the outcomes in colorectal cancer patients undergoing radicalresection by lowering the magnitude of inflammatoryresponses and modulating the immune response.