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Background. Pituitary adenomas (PAs) refers to a group of benign tumors that develop in the pituitary gland and are often characterized by fatigue. However, fatigue has not been documented in any Chinese research involving people with primary PA. The study sought to examine the prevalence, predictors, and correlation of fatigue with the quality of life (QoL) among PA patients in China. Methods. In total, 203 primary PA patients were included in this cross-sectional study. A series of questionnaires were administered, including the Multidimensional Fatigue Inventory (MFI), M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT), Short-Form 36 Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). Data analysis was accomplished by Pearson or Spearman correlations, linear regression, and simple path analysis. Results. Severe fatigue prior to the initial diagnosis and preparation for surgery affected 50% of PA patients. Depression, sleep disturbance, and MDASI-BT symptom total scores were independently able to predict patient fatigue. Sleep disturbance mediates the influence of depression on fatigue (IE sleep = 0.296, 95% CI: LB = 0.148 to UB = 0.471). Conclusions. Chinese patients with primary PA often report experiencing fatigue. Depression and poor sleep quality were shown to be significant contributors to PA patients' fatigue. Depression affects PA patients' fatigue directly or indirectly. Medical professionals should take a proactive approach to PA patients suffering from fatigue before initial diagnosis and preoperative preparation to determine necessary interventions early, thus reducing fatigue and ultimately enhancing their QoL. [ABSTRACT FROM AUTHOR]