OBJECTIVES: Patients with Systemic Lupus Erythematosus (SLE) experience unmet medical needs and many inflammatory symptoms resulting in humanistic and economic burden. This study aimed to create a conceptual model of patient and economic burden, and review patient-reported outcomes (PROs) used to measure such concepts in SLE clinical trials. METHODS: An SLE conceptual model was developed from structured review of published articles from 2007-June 2012 identified from literature databases (MEDLINE, PsycINFO, EconLit) plus other sources (PROLabels, FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptom/impact were identified from the literature. In the context of FDA guidance, the PROs were subject to in-depth review and assessed for face and content validity, and psychometric properties to determine appropriateness for use in SLE trials. RESULTS: Pain, fatigue, cognition, daily activities, emotional well-being, physical/social functioning, and work productivity were in the conceptual model identified as key SLE concepts. Of the 63 articles reviewed, 31 reported PRO data. From these and the other sources, 14 PROs were selected for review including SLE-specific health-related quality of life (HRQoL) measures (n=3), work productivity (n=1), and generic measures of fatigue (n=3), pain (n=2), depression (n=2) and HRQoL (n=3) as these were deemed salient for patients with SLE in the literature. The FACIT-Fatigue, BPI-SF (pain) and LupusQoL demonstrated the strongest face validity, conceptual coverage and psychometric properties measuring key concepts in the conceptual model. All PROs reviewed, except for the Lupus-specific HRQoL measures, lacked SLE patient involvement during development limiting their content validity. The HADS, SF-36v2, EQ-5D-3L and WPAI:Lupus showed suitability for SLE economic models. CONCLUSIONS: SLE is a condition associated with clear unmet medical needs and considerable burden to patients. This review highlights the current availability and future need for both disease-specific and generic patient-reported measures of relevant domains of disease signs and symptoms, HRQoL and work productivity.