Aims and objectives: To measure changes in health‐related quality of life, two dimensions of illness perceptions (i.e., consequences and emotional representations), fatigue and self‐efficacy in persons treated for colorectal cancer during the first year after surgical treatment, and to study how fatigue, illness perceptions and self‐efficacy measured at 3 months affect health‐related quality of life at 12 months postsurgery. Background: There are fluctuations in health‐related quality of life during the first year after treatment for colorectal cancer, and fatigue may negatively influence health‐related quality of life. Illness perceptions (consequences and emotional representations) and self‐efficacy have been shown to be associated with health‐related quality of life in other cancer diagnoses. Concerning colorectal cancer, there is a lack of knowledge concerning how illness perceptions and self‐efficacy change during recovery, and how these variables and fatigue at 3 months relate to health‐related quality of life at 12 months. Design: A prospective longitudinal design. Methods: Thirty‐nine persons surgically treated for colorectal cancer, of whom 17 had a colostomy, participated. Health‐related quality of life, fatigue, illness perceptions and self‐efficacy were assessed using QLQ‐C30, the Revised Illness Perception Questionnaire and the Maintain Function Scale. Descriptive and analytical statistics were used. Results: No changes were reported in levels of health‐related quality of life, fatigue or illness perceptions. Self‐efficacy was lower at 12 months compared to 3 months. Fatigue and one dimension of illness perceptions mediated the effect of self‐efficacy at 3 months on health‐related quality of life at 12 months. Conclusion: Persons treated for colorectal cancer who have lower self‐efficacy 3 months postsurgery are inclined to have more negative illness perceptions concerning emotions and to experience more fatigue. Relevance to clinical practice: Nurses need to support persons with fatigue and negative illness perceptions concerning emotions and to bolster their self‐efficacy, that is carry out follow‐up consultations focusing on illness management, symptoms, emotions and information on ways to increase self‐efficacy.