Seven hundred and two patients, 67 ± 12 years old, 71 % men, with distributions of New York Heart Association (NYHA) functional classes I/II/III/IV of 2/55/39/4 % were included in this cross-sectional analysis. Generic HRQoL was measured with the SF-36 health survey, disease-specific HRQoL with the Kansas City Cardiomyopathy Questionnaire, and depression with the self-reported Patient Health Questionnaire (PHQ-9). Both generic- and disease-specific HRQoL measurements indicated moderate to poor HRQoL. The KCCQ scores demonstrated higher sensitivity to the varying levels of heart failure severity as compared to the SF-36 scores. Patients with either a minor (15 %) or a major depression (24 %) reported significantly and substantially lower HRQoL (p < .001) than patients without depression did. In multivariable regression analyses, depression accounted for the largest part of the variance of both generic and specific HRQoL (12 and 36 %, respectively), whereas most biomedical variables had no or only a marginal influence.