Purpose: To explore for fatigue-related regions and the radiotherapy (RT) dose-fatigue relationship in nasopharyngeal cancer (NPC) survivors. Methods: Eighty disease-free NPC survivors completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN) after RT. Fatigue was evaluated by the MDASI-HN fatigue item (MDASI-HN-F) and Common Terminology Criteria for Adverse Events v3.0 (CTC-AE), between 6 and 36 months after RT to determine the presence of chronic fatigue. Skull base MRIs and planning CT/RT dose were retrievable for 56 patients. Dosimetric data were extracted for 10 MRI-defined potential fatigue at-risk structures (FARS): brainstem (BS), pituitary gland (PG), hypothalamus (HT), basal ganglia, internal capsule, pineal gland, sub-thalamic nuclei, thalamus, substantia nigra, and hippocampus (HC). Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic fatigue. Results: 56 pts formed the cohort. Thirty patients (54%) reported any fatigue per MDASI-HN-F. Thirty-three pts (59%) had any fatigue by CTC-AE. The maximum point doses (Dmax) for PG, BS, HC, and HT were numerically higher in patients with fatigue. Dmax and Dmean of the PG were significantly higher in patients with chronic fatigue, p ≤ 0.01. A dose-volume threshold of PG V52 Gy ≥16% (LogWorth 2.4, AUC 0.7) was identified on RPA, and potential sensitivity to the PG doses was observed in younger patients (<53 years-old). Conclusion: A dose-fatigue relationship was identified for the pituitary gland, both patient-reported and observer ratings. We recommend limiting the Dmax of PG to <54 Gy and V52 Gy to <16%, particularly in young NPC patients, during plan optimization when achievable.