Objective <p>To explore the potential profiles of cancer-related fatigue (CRF) in colorectal cancer patients and their relationship with exercise adherence.</p> Methods <p>A cross-sectional study was conducted with 329 patients with colorectal cancer in Wuhan, Hubei Province China from March to September 2024. Data were collected using general information questionnaires, the Cancer Fatigue Scale, and the Exercise Adherence Scale. Latent profile analysis was applied to explore the latent profiles of CRF. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between CRF profiles and exercise adherence.</p> Results <p>CRF in colorectal cancer patients can be categorized into three profiles: low CRF cognitively clear group (<i>n</i> = 138, 41.9%), moderate CRF balanced group (<i>n</i> = 165, 50.2%), and high CRF severe physical group (<i>n</i> = 26, 7.9%). Multivariate logistic regression analysis showed that living arrangements, recurrence and/or metastasis, the number of chemotherapies, and BMI were influencing factors for the profiles of CRF in colorectal cancer patients. There were statistically significant differences in the scores of various dimensions and the total score of exercise adherence among colorectal cancer patients with different profiles of CRF (<i>P</i> &lt; 0.05).</p> Conclusion <p>CRF in colorectal cancer patients can be divided into three profiles, and there are differences in exercise adherence among colorectal cancer patients with different profiles of CRF. It is recommended that healthcare professionals develop targeted interventions based on the different profiles of colorectal cancer patients to improve their exercise adherence and enhance their quality of life.</p>