Recent research evidence has shown that patients with chronic viral hepatitis develop symptoms of anxiety and/or depression, which has a strong impact on their health-related quality of life. This study aimed to assess the levels of anxiety, depression, and health-related quality of life among patients with chronic hepatitis B or C in Greece. It was a cross-sectional study among 111 patients with chronic viral hepatitis, evaluated at a tertiary General Hospital of Athens from March to September of 2014. Anxiety, depression, and health-related quality of life were assessed by the use of specially designed questionnaires. For the comparison between patients' population and general population, a pair-matched population of 111 healthy participants was recruited. Mean age of patients was 44.85 years (SD = 14.4). Fifty-nine patients were infected by hepatitis B virus and 52 by hepatitis C virus. Levels of anxiety and depression were higher among patients than among controls and the overall health-related quality of life was poorer (p < .001). Female gender and liver parenchyma damage were associated with higher levels of anxiety (p < .05). Certain demographic, socioeconomic, and clinical-serological factors were related with higher levels of depression. Poorer health-related quality of life was reported by patients with liver cirrhosis and alanine aminotransferase of 40 IU/L or more. Patients with chronic viral hepatitis demonstrate psychological and physical impairment, especially those with advance liver disease and/or active viral activity.