Abstract Objective: Cancer survivors who remain fatigued during long-term follow-up are at risk for worse health outcomes. To achieve personalized management of cancer-related fatigue, insight into its correlates among long-term survivors is needed to identify survivors at risk of remaining fatigued and also the correlates for intervention. Methods: Colorectal cancer (CRC) survivors diagnosed between 2000-2009, as registered in the population-based Eindhoven Cancer Registry, completed three annual surveys that included the Fatigue Assessment Scale, the EORTC Quality of Life (EORTC-QLQ-C30) questionnaire, Hospital Anxiety and Depression Scale, and physical activity levels. Linear mixed-model were used to assess the course of fatigue and identify its correlates. Results: 1734 (66%) CRC survivors completed at least 2 surveys. Fatigue levels were relatively stable over time. Being female, young (≤65 years old), single, low education, chemotherapy treatment, or having ≥1 comorbid condition was associated with higher fatigue scores. Years since diagnosis, radiotherapy treatment and disease stage were not related to fatigue scores. Significant between- and within-subjects effects were found for well-being factors (social, emotional, and cognitive function, and global quality of life), symptoms (anxiety, depression, pain, and insomnia) and functional status (physical and role function, and physical activity levels) in relation to fatigue. Differences in fatigue could be largely attributed to behavior/well-being (59%) and functional status (37%), and to some extent to sociodemographic (4%) and clinical (8%) factors. Conclusion: This study showed that behavior/well-being and functional status explained more variance in fatigue levels among CRC survivors than sociodemographic and clinical factors. Citation Format: Olga Husson, Floortje Mols, Lonneke van de Poll-Franse, Melissa Thong. The course of fatigue and its correlates in colorectal cancer survivors: A prospective cohort study of the PROFILES registry. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3731. doi:10.1158/1538-7445.AM2015-3731