Fatigue in childhood cancer is a pervasive and distressing symptom described as a "lack of energy". Carnitine is a micronutrient used to transport long chain fatty acids into muscle mitochondria. Some chemotherapy drugs interfere with the carnitine network. Both carnitine and fatigue relate to physical energy and may be influenced by chemotherapy. Using a repeated measures design, change in carnitine levels and change in fatigue in childhood cancer patients receiving ifosfamide, cisplatin, or doxorubicin were examined over multiple chemotherapy cycles. The influence of carnitine levels on fatigue was evaluated.Fifty-eight patients, between ages 3 and 18 years, within two months from diagnosis and receiving cisplatin, doxorubicin, and/or ifosfamide chemotherapy drugs, participated. Measurements included carnitine plasma levels and self-reported fatigue using established child or adolescent fatigue scales and were collected during the 2nd cycle of chemotherapy, and repeated on alternating cycles up to cycle 8. The Parent Fatigue Scale was used for children under age 7.Total and free carnitine levels did not change significantly for the group. Fatigue decreased significantly in children age 7-12 (p = 0.04). Relationships between fatigue and carnitine were not significant.Changes in carnitine plasma levels were not significant in this sample of patients. The carnitine levels remained within the reference values for children and were not associated with fatigue levels. School-age children may be more resilient to fatigue over the trajectory of treatment. Further research is needed into the biologic mechanisms of fatigue.