This study evaluates predictors of health-related quality of life (HRQoL) and fatigue in systemic sclerosis (SSc) using two novel self-report indices. A cross-sectional study of patients with SSc was undertaken using a postal questionnaire including the EuroQol-5Domain health questionnaire (EQ-5D™), Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) and the Scleroderma Health Assessment Questionnaire (SHAQ). The EQ-5D assesses five domains of health quality and is quantified as a time trade-off (TTO) value and patient global assessment (0-100 visual analogue scale [VAS]). The FACIT-F is a 13-item questionnaire (0-52 scale). Higher scores for both the EQ-5D and FACIT-F indicate better health. Case notes were scrutinised for patient demographics, disease duration, serology and clinical phenotype. Sixty-eight patients (60 females, mean age 62.6 years) completed the questionnaires. Fatigue correlated closely with HRQoL (r (s) = 0.78 and 0.77 for FACIT-F vs. EQ-5D VAS and TTO respectively, p < 0.01) and disability (r (s) = -0.74 for FACIT-F vs. HAQ-DI, p < 0.01). Pain was the most frequently reported health problem (80 %) in the EQ-5D. HRQoL also correlated closely with disability (r (s) = 0.83 for EQ-5D vs. HAQ-DI, p < 0.01). SHAQ-VAS scores correlated well with the FACIT-F, EQ-5D and HAQ-DI scores (p < 0.05 for all comparisons). Of the patient demographics and clinical disease associations, only the absence of upper gastrointestinal complications was associated with better levels of fatigue, HRQoL and function. There is a strong correlation between disability, fatigue and HRQoL measured using self-reports, possibly reflecting similarly perceived health beliefs amongst patients across outcomes. There was little association between self-report indices and patient demographics and/or clinical phenotype.