BACKGROUND Fatigue is an important clinical finding in patients with chronic hepatitis virus infection. However, studies assessing fatigue in patients with chronic hepatitis B (CHB) are very limited. This study aimed to quantify the severity of fatigue in patients with CHB, to determine whether perceived fatigue reflects impairment of functional ability, and to explore potential causes. METHODS A total of 133 patients with histologically proven CHB and 59 community controls were assessed using the fatigue impact scale (FIS). RESULTS The degree of fatigue was significantly higher in patients with CHB than in controls (mean (range) FIS 24.9 (0-91) vs. 15.7 (0-31), p < 0.001). Fatigue experienced by patients with CHB was similar to that in primary biliary cirrhosis (PBC) (n = 20) (FIS 22.2 vs. 20.9, p = 0.28). No association was found between FIS and biochemistry and histological parameters of liver disease severity. Significant associations were found between fatigue severity and cognitive impairment (r = 0.39, p < 0.001), daytime somnolence (r = 0.32, p < 0.001), scores of the Chronic Liver Disease Questionnaire (r = - 0.31, p < 0.001), and autonomic symptoms (r = 0.43, p < 0.001). The level of autonomic symptom was the only factor independently associated with the degree of fatigue. CONCLUSIONS Fatigue is a significant problem of functional ability impairment in CHB and similar in degree to that in PBC patients. Fatigue in patients with CHB appears to be unrelated to the severity of liver disease but is associated with significant autonomic symptoms.