Background: Fatigue is one of the most distressing symptoms among breast cancer survivors (BCS) after finishing their treatment. Besides cancer-related factors, fatigue may be influenced by socio-demographic, physical, medical, psychological and behavioural variables. Exercise is recommended to manage CRF. Methods: PH-UEM02 and PH-UEM06 were prospective observational studies in BCS after finishing their treatments. Fatigue was evaluated through the Perform Questionnaire (12-60, being 60 no fatigue). Anthropometry, physical condition (PC) and physical activity (PA) were objectively evaluated. One-mile walk test (MWT), handgrip and sit to stand were used to assess PC. PA was measured by using accelerometers. Clinical data (treatments) were obtained from the clinical record. Socio-economic, diet (PREDIMED questionnaire) and QoL (EORTC QLQ-C30) were reported by BCS. Results: 201 BCS were recruited (age 51±9, BMI 25.9±4, median time from diagnosis 22 months). 73% had been treated with chemo, 66% anthracyclines, 20% trastuzumab, 66% radiotherapy, 81% hormone (24% aromatase inhibitors). Mean PERFORM score (45.6/60). Adherence to Mediterranean diet (9.1/14). EORTC Global score (68.9/100). No association with age, socio-economic or marital status, previous chemo, anthracyclines or radiotherapy, WPA, estimated VO2max, handgrip, sit to stand or PREDIMED score was found. Weight, trastuzumab and MWT time were positively associated with fatigue (<.05). Time from diagnosis, basal and recovery heart rate, global QOL-EORTC were negatively associated. An interesting negative association with nut intake was found (<.05). 42% had a fatigue score (< 45) associated with QOL scores under the normative values for the Spanish population. Conclusions: 1. Prevalence of significant CRF in mid-term BCS is around 40%. Weight was a positive predictor. CRF diminishes along the time and has a strong impact on QoL. 2. Regarding PC/PA, only the time spent in MWT predicted fatigue. Neither WPA, estimated VO_2MAX or muscular strength were associated with fatigue. 3. Regarding previous treatments, only trastuzumab was associated with CRF. 4. Interestingly heart rate (both basal and recovery) and nut intake were strongly associated with CRF. 5. More research is warranted in heart rate variability and potential related biomarkers.