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Background and Aims A chronic feeling of fatigue occurs in up to 85% of childhood cancer survivors (CCS). This phenomenon has a detrimental effect on quality of life, reintegration in daily life activities and psychosocial functioning of the patient. Therefore, it is important to elucidate potential individual risk and protective factors. Methods CCS who were treated in the University Hospital of Leuven, completed two annual questionnaires on cancer‐related distress (fear of cancer recurrence and post‐traumatic stress, resilience and fatigue). Associations between distress and fatigue levels were examined by performing cross‐lagged panel analyses. Resilience was included as a potential moderator. These models included all within‐time associations, stability paths, and cross‐lagged paths. Gender and time since diagnosis were included as covariates. Results In total, 110 CCS participated in this study, aged 14–25 years (average time since diagnosis 12.2 years; 41.8% boys; diagnosed with leukemia/lymphoma [49%], solid tumor [15%], brain tumor [16%] or other [20%]). Fear of cancer recurrence and post‐traumatic stress at baseline positively predicted fatigue 1 year later. Cross‐lagged panel analyses showed that resilience did not buffer the effect of fear of cancer recurrence on fatigue, in contrary to our expectations. Stability coefficients were high for all study variables. Conclusion This study indicates associations between cancer‐related distress (fear of cancer recurrence and post‐traumatic stress), resilience and cancer‐related fatigue over time in CCS. Interventions to improve fatigue levels could be focusing on both tackling cancer‐related distress, while improving resilience levels as well.