The use of education is recommended to teach patients self-care behaviours to reduce cancer-related fatigue, however, there is little evidence of its effectiveness or optimal timing. This educationally based cancer-related fatigue intervention trial, CAN-FIT, aimed to reduced severity of fatigue in radiotherapy patients.One hundred and ten participants aged≥18 years undergoing curative radiotherapy were randomly assigned to receive (1) pre- and post-radiotherapy fatigue education and support (RFES); (2) pre-RFES only; (3) post-RFES only; or (4) no RFES (standard care). Data collection occurred at pre- and post- radiotherapy and at 6-weeks follow-up.The intervention was not associated with reduction in fatigue levels at any assessment point. Significant changes were seen with secondary activity-based outcomes: Physical activity participation: Pre-RFES was associated with significantly greater increase in vigorous [Assessment (Ax)1-Ax2: 1.05 (0.24, 1.86) p<0.01: Ax2-Ax3: 1.24, (0.44, 2.03) p<0.01] and moderate physical activity participation [Ax1-Ax2: 1.4 (0.53, 2.26) p<0.01]. Post-RFES was associated with significant improvements in walking levels [Ax1-Ax3: 5.82 (0.07, 11.56) p<0.05] compared with no pre-RFES. Paid and unpaid employment: Pre-RFES was associated with slower return to pre-treatment levels of paid work [Ax2-Ax3: -0.72 (-1.41, -0.04) p<0.05] than no pre-RFES. Post-RFES was associated with decreased levels of unpaid work [Ax1-Ax3: 561.79 (51.21, 1,072.37) p<0.05] compared with no post-RFES.The CAN-FIT programme did not significantly improve the primary outcome, level of fatigue, regardless of when it was delivered, however, significant changes were observed in activity-based outcomes. Further investigations into educationally based programmes should target activity participation rather than changes in underlying fatigue to improve overall patient health.