Abstract Background Patients’ objectives and experiences must be core to the study and management of chronic diseases, such as SSc. Although patient-reported outcomes are attracting increasing attention, evaluation of the impact of disease on the overall subjective well-being, equivalent to ‘happiness’, is remarkably lacking. Objectives To examine the determinants of happiness and quality of life in patients with SSc, with emphasis on disease features and personality traits. Methods Observational, cross-sectional multicentre study, including 142 patients, with complete data regarding disease activity, disease impact, personality, health-related quality of life (HR-QoL) and happiness. Structural equation modelling was used to evaluate the association between the variables. Results The results indicated an acceptable fit of the model to the data. Perceived disease impact had a significant negative direct relation with HR-QoL (β = −0.79, P < 0.001) and with happiness (β = −0.52, P < 0.001). Positive personality traits had a positive relation with happiness (β = 0.36, P = 0.002) and an important indirect association upon QoL (β = 0.43) and happiness (β = 0.23). Perceived disease impact is influenced by body image, fatigue and SSc-related disability to a higher degree (β = 0.6–0.7) than by disease activity (β = 0.28) or form (β = 0.17). Impact of disease had a much stronger relation with HR-QoL than with happiness. Conclusions The results suggest that treatment strategies targeting not only disease control but also the mitigation of relevant domains of disease impact (body image, fatigue, global disability) may be important to improve patients’ experience of the disease. The reinforcement of resilience factors, such as positive psychological traits, may also play a contributory role towards better patient outcomes.