Fatigue is a common symptom in patients with ankylosing spondylitis (AS). However, fatigue of AS patients has not been well elucidated in China. This study aimed to evaluate the predictors of fatigue and the effects of fatigue on health-related quality of life among patients with AS.A total of 150 AS patients were involved in the study. A series of questionnaires included the following: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), the 10-cm Visual Analog Scale (VAS), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Pittsburgh Sleep Quality Index (PSQI), the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Short Form 36 Health Survey (SF-36), and the Fatigue Severity Scale (FSS). Independent samples t test, Mann-Whitney U test, chi-square analysis, Pearson/Spearman correlation, and binary logistic regression were used to analyze the data.The results demonstrated that 48.7% individuals with AS suffered from fatigue. Binary logistic regression indicated that waist-to-hip ratio, BASDAI, and sleep disturbance were independent predictors of fatigue in AS patients. Meanwhile, severe fatigue led to lower quality of life.These findings suggested that medical personnel should pay more attention to AS patients with fatigue and take effective measures to relieve fatigue.Key Points• Incidence of fatigue in AS patients is 48.7% according to this cross-sectional study.• The occurrence of fatigue was associated with higher WHR, higher BASDAI, and sleep disturbance.• We also found that the occurrence of fatigue significantly reduced the quality of life in AS patients both physically and psychologically.