This analytical, cross-sectional study aimed to analyze the relationship between depressive symptoms, appetite, and quality of life (QoL) in 86 patients hospitalized with heart failure. Patients were assessed for depressive symptoms, appetite, and QoL using the Beck Depression Inventory-II, the Simplified Nutritional Appetite Questionnaire, and the Minnesota Living with Heart Failure Questionnaire, respectively. Relationships between sociodemographic and clinical variables, depressive symptoms, appetite, and QoL were analyzed using bivariate tests and linear regression models, with p < .05 considered significant. The factors associated with QoL were dependence for four activities of daily living (ADLs) (estimate = 15.4, 95% CI = 0.23 to 30.64, p = .046), minor depressive symptoms (estimate = –20.0, 95% CI = –28.3 to −11.73, p < .001), and appetite (estimate = –11.08, 95% CI = –20.5 to −1.62, p = .022). These results can support multi-professional assessment and development of interventions to promote better QoL, including addressing impaired appetite and food intake, the presence or increased intensity of depressive symptoms, especially in patients dependent for ADLs.