PURPOSE: Advances in cancer treatment have increased childhood cancer patient's survival rates. However, many childhood cancer survivors (CCS) face long-term effects such as fatigue. This study assessed fatigue in CCS and healthy controls (HCs), its contributors, and associated outcomes. METHODS: This cross-sectional study included 90 CCS and 55 age and sex-matched HCs. Fatigue was measured using the Pediatric Quality of Life Multidimensional Fatigue Scale, and modifiable contributors included sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and physical fitness (VO RESULTS: General, cognitive, and total fatigue were significantly higher in CCS compared to HCs (44.7% vs. 23%, p <
.001
cognitive: 64.7% vs. 29.3%, p <
.001
total fatigue: 56.5% vs. 25%, p <
.001). Sex, PSQI, PSQI × sex, and PSQI × VO₂ were significant predictors for general fatigue, PSQI and PSQI × VO₂ for cognitive fatigue, and PSQI for sleep/rest and total fatigue. Cognitive and total fatigue correlated most strongly with cognitive and work-related functioning, whereas general and sleep/rest fatigue were more related to psychosocial functioning. CONCLUSION: Fatigue is highly prevalent among CCS, with distinct factors influencing general, sleep/rest, cognitive, and total fatigue. Female survivors, those with poorer sleep quality and lower physical fitness, are at risk. IMPLICATIONS FOR CANCER SURVIVORS: This study underscores the need for tailored interventions for each type of fatigue. Improving sleep quality, physical fitness, and psychological well-being may contribute to reducing fatigue and enhancing overall quality of life in CCS.