Introduction: LupusQoL is a questionnaire specifically designed to assess health-related quality of life (HRQoL) in SLE patients. We report on the translation and cross-cultural adaptation of LupusQoL into European Portuguese. Methods: Translation and cultural adaptation were performed according to standard protocol described by the original developers. LupusQoL-PT was administered to patients during a routine visit from an outpatient clinic at a university hospital in Portugal. Content structure was validated using factorial analysis. Cronbach’s alpha coefficient was computed for internal consistency. Sociodemographic were questioned during the visit and clinical data were collected during the visit and from the clinical files. Pearson’s correlation, T-test, Mann-Whitney and one-way ANOVA were applied to test internal and external validation. Results: Seventy-nine SLE patients (78 woman: 1 man) were evaluated. Most had Low disease activity (mean SLEDAI-2k = 3.49; standard deviation 4.80), 19% had moderate to severe activity and 38% had damage accrual (mean SDI = 0.75; standard deviation 1.05). Cronbach’s alpha coefficient was at least 0.812, confirming good internal consistency. Correlation coefficient and test-retest correlation between the eight domains of LupusQoL-PT were strong in almost every domain (p < 0.01). External convergent analysis showed strong correlation between LupusQoL-PT and Medical Outcome Study Short Form 36-item version 2 and visual analogic scale. Current disease activity was negative correlated with “Body Image” domain. There was no correlation between other LupusQoL-PT domains and SLEDAI-2k on divergent validity. Patients with previous neuropsychiatric and DMARDs treatment had lower HRQoL in emotional domains, while patients with renal damage accrual had HRQoL impact in both physical and emotional domains. Portuguese SLE patients had lower HRQoL than French and Italian validation cohorts’ patients, and higher than Spanish cohorts. Conclusion: LupusQoL-PT has shown adequate metric properties and should be considered an appropriate tool to evaluate HRQoL in Portuguese SLE patients.