Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients.Materials and Methods:A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery.Results:Preoperative cognitive functioning scores (95% CI 0.131–1.158,p= 0.015) and low anterior resection (95% CI 14.861–63.260,p= 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = −0.277,p= 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99;p= 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = −0.620, 95% CI −1.073–−0.167,p= 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961,p= 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129,p< 0.001) were statistically significant.Conclusions:Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.