ABSTRACT: Background:Although fatigue is a common and distressing symptom in cancer survivors, the mechanism of fatigue is not fully understood. Therefore, this study aims to investigate the relation between the fatigue and mindfulness of breast cancer survivors using anxiety, depression, pain, loneliness, and sleep disturbance as mediators. Methods:Path analysis was performed to examine direct and indirect associations between mindfulness and fatigue. Participants were breast cancer survivors who visited a breast surgery department at a university hospital in Japan for hormonal therapy or regular check-ups after treatment. The questionnaire measured cancer-related-fatigue, mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance. Demographic and clinical characteristics were collected from medical records. Results:Two-hundred and seventy-nine breast cancer survivors were registered, of which 259 answered the questionnaire. Ten respondents with incomplete questionnaire data were excluded, resulting in 249 participants for the analyses. Our final model fit the data well (goodness of fit index?=?.993; adjusted goodness of fit index?=?.966; comparative fit index?=?.999; root mean square error of approximation?=?.016). Mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance were related to fatigue, and mindfulness had the most influence on fatigue (??=?- .52). Mindfulness affected fatigue not only directly but also indirectly through anxiety, depression, pain, loneliness, and sleep disturbance. Conclusions:The study model helps to explain the process by which mindfulness affects fatigue. Our results suggest that mindfulness has both direct and indirect effects on the fatigue of breast cancer survivors and that mindfulness can be used to more effectively reduce their fatigue. It also suggests that health care professionals should be aware of factors such as anxiety, depression, pain, loneliness, and sleep disturbance in their care for fatigue of breast cancer survivors. Trial registration:This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN number. 000027720) on June 12, 2017.