<p>Insulin resistance and stress response are relatively prevalent among patients with colorectal cancer before surgery. This study aimed to explore the effects of these two disorders on the risk of anastomotic leakage after colorectal cancer surgery. Briefly, 503 patients with this type of cancer scheduled for surgery were enrolled. The study used the HOMA-IR to evaluate the patients’ preoperative insulin resistance, collected blood samples to detect the preoperative levels of adrenaline and cortisol, and also adopted the State-Trait Anxiety Inventory and the Impact of Event Scale to assess the patients’ psychological stress status. After performing the surgery, the study monitored the onset of anastomotic leakage within one month. Multivariable logistic regression was used for data analysis. The results suggested that preoperative insulin resistance, elevation of the two hormone levels, and increased psychological stress scores were significantly associated with an increased risk of anastomotic leakage. When the levels of adrenaline and cortisol increased by one standard deviation, the increase in the risk of this postoperative complication was greater in patients with insulin resistance than in those without insulin resistance. In conclusion, both preoperative insulin resistance and stress response were potential risk factors for anastomotic leakage after colorectal cancer surgery.</p>