Background: Fatigue after breast cancer treatment is a major health problem that is very difficult to treat. Our aim was to determine whether the early introduction of focused rehabilitation from the start of the cancer treatment is associated with the frequency of fatigue in breast cancer patients. Methods: The subjects of our prospective study were 600 female breast cancer patients (26-65 (mean 52) years of age), who participated in the pilot study on the individualized integrated rehabilitation of breast cancer patients in 2019-2022 and were followed for at least six months. The control group included 300 patients and the intervention group 300 patients. The patients completed three questionnaires (EORTC QLQ - C30, B23 and NCCN): before and six months after the beginning of cancer treatment. The control group obtained the same rehabilitation as was offered to all breast cancer patients in our hospital before the start of our study. The multidisciplinary rehabilitation team reviewed the documentation of all the patients from the intervention group before six months after the beginning of treatment and recommended appropriate interventions according to the patient's problems. The integrated rehabilitation coordinator referred patients for additional treatments in compliance with the institute’s new clinical pathway (psychologist, general practitioner, nutritional treatment, physical rehabilitation, kinesiologist-guided online exercises, gynaecologist, analgesia, vocational rehabilitation). Data on the patients’ demographics, disease extent, cancer treatment and complaints reported in questionnaires were collected. This data and the frequency of fatigue six months after the beginning of treatment in both groups of patients were analysed using the chi-square and ANOVA test. Results: There were no differences between the control and the intervention group of patients in terms of age, education, disease extent, surgical procedures, systemic cancer treatment, or radiotherapy. There were no differences between the groups in the prevalence of fatigue before the start of treatment. Before the cancer treatment, 50% of the patients in both groups reported fatigue, while moderate or severe fatigue was reported in the intervention and control groups in 9% and 10% (p = 0.69), respectively. Six months after the beginning of cancer treatment, fatigue was reported in the intervention and control groups in 66% and 70% (p = 0.38), respectively. However, moderate or severe fatigue were reported in the intervention and control groups in 17% and 26% (p = 0.02), respectively. Conclusions: Early integrated rehabilitation is associated with a lower prevalence of moderate or severe fatigue in breast cancer patients in comparison to the control group six months after the beginning of cancer treatment.