Objective To study the effect of indirect calorimetry-guided nutritional support on energy metabolism, cellular immunity and oxidative stress in patients with colorectal cancer after laparoscopic surgery. Methods A total of 96 patients with colorectal cancer after laparoscopic surgery in our hospital from December 2019 to December 2021 were selected and randomly divided into the control group (used the formula prediction method to guide enteral nutrition support, n=48) and the observation group (used indirect calorimetry to guide enteral nutrition support, n=48). The target resting energy expenditure (REE) value and nutritional support energy intake were compared between the two groups. The cellular immune indexes (CD3+, CD4+, CD8+, CD4+/CD8+) and oxidative stress indexes [serum superoxide dismutase (SOD), malondialdehyde (MDA), the changes of glutathione peroxidase (GSH-Px)], and the changes of REE at different time points (1 day before operation and 1, 2 and 3 days after operation) of the two groups were compared. The incidence of complications in the two groups were observed. Results The target REE value of the observation group was lower than that of the control group (P＜0.05), and there was no significant difference in the enteral energy intake and parenteral energy intake compared with the control group (P＞0.05). After treatment, CD3+, CD4+ and CD4+/CD8+ in the two groups were lower than those before treatment (P<0.05), and CD8+ was higher than before treatment (P<0.05). The levels of CD3+, CD4+ and CD4+/CD8+ in the observation group after treatment were higher than those in the control group (P<0.05) , while the level of CD8+ in the observation group was lower than that in the control group (P<0.05). After treatment, the levels of SOD and GSH-Px in the two groups were lower than those before treatment (P<0.05), and the levels of MDA were higher than those before treatment (P<0.05). The levels of GSH-Px and SOD in the observation group were higher than those in the control group (P<0.05), while the level of MDA in the observation group was lower than that in the control group (P<0.05). There was no significant difference in the REE value between the two groups at 1 day before operation (P>0.05); compared with the 1 day before operation, the REE values of the two groups at 1, 2, and 3 days after operation were significantly increased, and there was a statistically significant difference between the two groups at each time point (P<0.05), but the REE value at 3 days after operation was significantly lower than that at 1 and 2 days after operation (P<0.05). The REE values in the observation group were lower than those in the control group at 1, 2 and 3 days after operation (P<0.05). The incidence of complications in the observation group was 6.25%, which was lower than 20.83% in the control group (P<0.05). Conclusion Enteral nutrition support guided by indirect calorimetry in colorectal cancer patients after laparoscopic surgery can help reduce postoperative energy consumption, improve cellular immune function and oxidative stress response, and reduce the risk of postoperative complications, which is worthy of promotion.