Objective: The aim of the current study was to evaluate changes in treatment outcomes in terms of healthrelated quality of life (HRQoL) and symptom burden at zero, one, three, and six months after an initial diagnosis of colorectal cancer. The demographic and clinical characteristics that account for outcome changes in patients were investigated using a repeated measures framework. Methods and Materials: A cohort study was performed of 134 colorectal cancer patients followed from diagnosis to 6 months post-treatment in Central Taiwan. HRQoL and symptoms were assessed at diagnosis and one, three, and six months thereafter. The Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire, VAS pain, and the Memorial Symptom Assessment Scale (MSAS) were used for data collection. A generalized estimating equation (GEE) was applied for statistical analysis. Results: The majority of the patients were male (55%) and married (91.5%). The mean age was 60.4 years (SD = 11.71). Most were diagnosed stage III and IV colorectal cancer (54.5%). All underwent surgery; some also received chemotherapy (CT) or concurrent chemoradiation therapy (CCRT). The results of the GEE showed that overall, the HRQoL, pain, and symptoms of the patients significantly improved over the treatment period. Patients with stage IV disease who had received surgery and CCRT showed the worst HRQoL. Females, patients with comorbidity, and stage IV patients had higher pain scores over time. Female and stage IV patients had more severe physical symptoms, whereas stage II and IV patients had worse psychological symptoms over time. Conclusion: The patients' HRQoL, pain, and symptoms significantly improved over the 6-month treatment period. Certain patient and clinical variables accounted for changes in treatment outcomes regarding HRQoL and symptom burden in colorectal cancer patients.