The BNI (2 sessions) focused solely on increasing and maintaining physical activity during cancer treatment. The CBT (6 sessions) focused additionally on regulating the sleep-wake cycle, accepting the consequences of cancer and treatment, managing the experience of cancer in relation with others, and challenging to make future plans. The CBT group was significantly less fatigued after cancer treatment compared to the UC, but no difference was found between BNI and UC (ANCOVA). Mediation analysis showed that none of the physical activity measures mediated the reduction in fatigue realised by CBT. Conclusion: CBT proved to be effective in reducing fatigue during cancer treatment. Physical activity had no mediating role in the effect of CBT. Thus, our findings indicate that with CBT it was possible to realize a significant reduction in fatigue without a lasting increase in physical activity. Funding provided by the Dutch Cancer Society.