Using cross-sectional data from a representative sample of the French population (the 2008 Disability Health survey), this paper examines whether the SF-6D, a widely used preference-based measure of health-related quality of life in economic evaluations, fully captures the variation in subjective well-being (SWB) due to chronic illnesses. We conduct a mediation analysis to disentangle the direct and indirect, through the SF-6D, effects of various chronic conditions on SWB (happiness). Our results show that the SF-6D reflects changes in happiness due to most illnesses except mental illness. Changes in SWB mediated by the SF-6D account for 74% of the total effect. The variation unexplained by the SF-6D is significant and increases substantially in the presence of multimorbidity when a chronic illness is combined with anxiety or depression. Overall, our results suggest that the SF-6D incompletely captures the subjective experience of chronically ill patients, especially those with comorbid conditions.