This study aimed to describe the impact of mutuality, anxiety, and depression on quality of life (QoL) in patients with heart failure (HF) using cross-sectional, convenient, and consecutive sampling. A total of 97 patients were recruited. Socio-demographic and clinical variables and self-report measures of anxiety, depression, mutuality, and QoL were collected. The results highlighted the pivotal role of mutuality (specifically the domain of shared values between patients and their caregivers) in determining perceptions of physical health. Conversely, depression was a negative determinant of perceptions of both physical and mental health. Future research is needed to describe in-depth and longitudinally the associations between mutuality and QoL in patients with HF.