To compare immunonutrition versus standard high calorie nutrition in patients undergoing elective colorectal resection within an Enhanced Recovery After Surgery (ERAS) program.Despite progress in recent years in the surgical management of patients with colorectal cancer (ERAS programs), postoperative complications are frequent. Nutritional supplements enriched with immunonutrients have recently been introduced into clinical practice. However, the extent to which the combination of ERAS protocols and immunonutrition benefits patients undergoing colorectal cancer surgery is unknown.The SONVI study is a prospective, multicenter, randomized trial with 2 parallel treatment groups receiving either the study product (an immune-enhancing feed) or the control supplement (a hypercaloric hypernitrogenous supplement) for 7 days before colorectal resection and 5 days postoperatively.A total of 264 patients were randomized. At baseline, both groups were comparable in regards to age, sex, surgical risk, comorbidity, and analytical and nutritional parameters. The median length of the postoperative hospital stay was 5 days with no differences between the groups. A decrease in the total number of complications was observed in the immunonutrition group compared with the control group, primarily due to a significant decrease in infectious complications (23.8% vs. 10.7%, P = 0.0007). Of the infectious complications, wound infection differed significantly between the groups (16.4% vs. 5.7%, P = 0.0008). Other infectious complications were lower in the immunonutrition group but were not statistically significantly different.The implementation of ERAS protocols including immunonutrient-enriched supplements reduces the complications of patients undergoing colorectal resection.This study is registered with ClinicalTrial.gov: NCT02393976.