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Survivors of childhood cancer are prone to an increased risk of chronic issues such as cardiovascular disease, fatigue, weight-related problems, and emotional disturbances.This study utilized the biopsychosocial model to examine the hypothesis that greater depression and lower mobility would be significantly associated with greater fatigue and higher body mass index in survivors of childhood cancer.Data were analyzed for 144 children treated and followed up for an oncology condition at a southeastern academic medical center. Voluntarily, children completed the Patient-Reported Outcomes Measurement Information System 1.0, and parents completed the Family Symptom Inventory as part of a brief annual psychosocial screening battery. Height and weight were collected by a clinic nurse prior to questionnaire completion.Hierarchical linear regression showed that shorter time since diagnosis (β = −.154, P < .05), greater child-reported depression (β = .396, P < .01), and lower mobility (β = .427, P < .01) significantly predicted greater fatigue (adjusted R2 = 0.54). Older age (β = .262, P < .01) and not receiving chemotherapy (β = −.209, P < .05) significantly predicted higher body mass index (adjusted R2 = 0.051).Findings showed that fatigue tends to improve over time after treatment but may be predicted by greater depression symptoms and lower mobility in recent survivors of childhood cancer.For survivors of childhood cancer with higher levels of fatigue, treating symptoms of depression and maximizing physical and mobility may be of clinical value. With the impact of psychological and social factors not yet understood in pediatric cancer survivors, weight status in recent survivors of childhood cancer is likely a complex interaction between biological and treatment factors.