Colorectal cancer (CRC) treatment is associated with a high morbidity which may result in a reduced health-related quality of life (HRQoL). The pre-operative measurement of handgrip strength (HGS) might be a tool to predict the patient’s outcome after CRC surgery. The aim of this study was to evaluate the association of pre-operative HGS with the occurrence of postoperative complications and postoperative HRQoL. Stage I to III CRC patients ≥ 18 years were included at diagnosis. Demographic and clinical data as well as HGS were collected before start of treatment. HGS was classified as weak if it was below the gender-specific 25th percentile of our study population; otherwise HGS was classified as normal. The occurrence of postoperative complications within 30 days after surgery was collected from medical records. Cancer-specific HRQoL was measured 6 weeks after treatment using the EORTC QLQ-C30 and the EORTC QLQ-CR29 questionnaire. Of 295 patients who underwent surgical treatment for CRC, 67 (23%) patients had a weak HGS while 228 (77%) patients had normal HGS. 118 patients (40%) developed a postoperative complication. Complications occurred in 37% of patients with a weak HGS and in 41% of patients with a normal HGS (p = 0.47). After adjustment for age, sex, ASA, BMI and TNM, no significant associations between pre-operative HGS and the occurrence of postoperative complications and between HGS and HRQoL were found. We conclude that a single pre-operative HGS measurement was not associated with the occurrence of postoperative complications or post-treatment HRQoL in stage I-III CRC patients.