Objective: The purpose of this case report was to describe the examination and management of a patient with chronic fatigue. Clinical Features: A 34-year-old woman presented to a chiropractic clinic with complaints of fatigue and inability to lose weight for 2 years. When tested, she was found to have high serum thyroglobulin antibodies, low serum vitamin D 3 , low saliva dehydroepiandrosterone-sulfate, and low saliva total and diurnal cortisol. Intervention and Outcome: The patient was placed on an anti-inflammatory ancestral diet and given recommendations to decrease the aerobic intensity of her exercise routine. On the basis of the result of conventional and functional laboratory tests, she was prescribed a treatment plan of targeted supplementation. After 12 weeks of application of dietary, lifestyle, and supplementation recommendations, the patient reported experiencing increased energy and weight loss of 15 pounds. Her thyroglobulin antibodies returned within reference range, salivary cortisol increased and closely followed the proper circadian rhythm, and dehydroepiandrosterone-sulfate increased. Conclusions: This report describes improvement in a patient with chronic fatigue with the use of nonpharmaceutical polytherapy involving dietary changes, lifestyle modification, and supplementation. (J Chiropr Med 2016;15:314-320)