Objective: To compare influences between laparoscopic and open surgery on humoral immune function and energy metabolism in acute cholecystectomy. Methods: Sixty patients with acute calculous cholecystitis were randomly designated to observational group and control group with 30 cases in each group. Patients in observational group underwent laparoscopic cholecystectomy and those in control group were subjected to open cholecystectomy. The surgery-related parameters, and indexes associated with the changes in immune function, energy metabolism and nutrient loss in the two groups were compared. Results: The operative time, intraoperative blood loss, and time to first postoperative flatus and ambulation in observational group were significantly reduced compared with control group (all P<0.05). The levels of IgG, IgM, IgA, C3, C4 and IL-4, and values of resting energy expenditure (REE) and respiratory quotient (RQ) in both group were all decreased significantly compared with the preoperative ones, but the decreasing degrees in all the above parameters were less and the duration of their decreases were shorter in observational group than those in control group (all P<0.05). The levels of albumin (ALB) and transferrin (TRF) and the values of triceps skinfold thickness (TSF) and arm muscle circumference (AMC) in both groups at postoperative day 7 were all decreased significantly compared with the preoperative ones, but their decreasing amplitudes were all significantly less in observational group than those in control group (all P<0.05). Conclusion: Laparoscopic procedure for acute cholecystectomy has superior efficacy than open surgery, and it also has the advantages of lessened immune function alterations and reduced energy loss.