Background Social support, family functioning and family health are essential elements in the treatment of heart failure, yet most heart failure studies focus on the pharmacological interventions. This study aimed to examine whether perceived social support from nurses is associated with better family functioning of patients with heart failure and their nearest relatives and to examine whether family health mediates this relationship. Methods and findings A sample of 312 patients with heart failure and 312 of their nearest relatives were included in the study. The Family Functioning, Health and Social Support questionnaire was used to collect the data. Dyadic data were analysed by the Actor–Partner Interdependence Mediation Model with distinguishable dyads using structural equation modelling. Patients and nearest relatives who perceived more social support had a higher level of family health and functioned better within the family. One partner effect was found, indicating that the higher the level of family health of the nearest relative, the better the family functioning of the patient (p <0.001). Family health partially (in the patient) and completely (in the nearest relative) mediated the association between social support and family functioning. Conclusion This study indicated that patients with heart failure and their nearest relatives who perceived more social support from nurses were more likely to have high level of family health and function better within the family. The interdependent relationships found in our study highlight a dyadic and family-oriented approach to improve family functioning in patients with heart failure.