Background: Dynamic changes of cancer-related fatigue (CRF) among hospitalized patients with colorectal cancer were determined. Materials and Methods: This longitudinal, descriptive study involved 96 hospitalized patients with colorectal cancer, all recruited from a tertiary general hospital in Guangzhou, China. Patients completed questionnaires three times to assess the degree of fatigue, and measurement points were within one week of admission, at 2 to 3 days after surgery and 3 weeks after surgery. Results: Significant differences among the three measurement points (p<0.01) were observed. The scores of fatigue in the second survey were the highest, followed by the third and first surveys. Colon cancer patient scores were higher than those of rectal cancer patients with a significant difference (p<0.05). Colorectal patients experienced different degrees of fatigue at different periods during hospitalization. Conclusions: This study highlights the importance of interventions that are carefully tailored to patients based on the characteristics at different periods to alleviate fatigue.