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Abstract Background A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil. Methods This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources. Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE. Results Overall, 300 patients with SLE were included (92.3% female, mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001). Conclusion These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country. (COI whole (SLE Brazil 12month, 12month month 12 month, 12-month crosssectional, crosssectional cross sectional, sectional cross-sectional ACR 199 Criteria questionnaires (questionnaires records covering profile morbidities 12Item Item Survey SF12, SF12 SF , SF-12) healthrelated health related consultations, consultations (consultations tests medications hospitalization nonhealthrelated non transportation, transportation (transportation adaptation caregivers consumed Overall 30 92.3% 923 92 3 (92.3 female standard SD 118 11 8 11. 7.9 79 7 9 [7.9 years, years years) 10 33.3% 333 33 (33.3% SLErelated 4 15.3% 153 15 (15.3% schooling (SD 44 4. 12.6 126 6 (12.6 hours 222 (22 74.0%. 740 74.0% . 74 0 [74.0%]) SF-1 ( 0117 117 0.117 0.042, 0042 0.042 042 0.042) CollaboratingClinicsAmericanCollegeofRheumatology CollaboratingClinics AmericanCollegeofRheumatology 0115 115 0.115 0.046, 0046 0.046 046 0.046) medicationsday day comorbidities co 0272 272 0.272 0.001, 0001 0.001 001 0.001) SLEspecific specific drugsday 0113 113 0.113 0.051, 0051 0.051 051 0.051) 0570 570 0.570 0.001. 0232 232 0.232 US312353patientyear USpatientyear US 123 53 year interquartile IQR US161851 1 618 51 US$1,618.5 $678.66, 67866 678 66 [$678.66 $4,601.29. 460129 $4,601.29 601 29 $4,601.29]) medication (IQR US91062 910 62 US$910.6 $460, 460 ($460 $4,033.51. 403351 $4,033.51 033 $4,033.51) 3664 664 3.66 erythrocyte Creactive C reactive protein 0381 381 0.38 biological social factors decisionmaking decision making country 19 SF1 92.3 (92. 7. [7. 33.3 (33.3 15.3 (15.3 12. (12. 22 (2 74.0 [74.0%] SF- 011 0.11 004 0.04 04 027 27 0.27 000 0.00 00 005 0.05 05 057 57 0.57 023 23 0.23 patientyear 5 US16185 61 US$1,618. $678.66 6786 67 [$678.6 46012 $4,601.2 60 2 $4,601.29] US9106 91 US$910. $460 ($46 40335 $4,033.5 03 366 3.6 038 38 0.3 92. (92 [7 33. (33. 15. (15. (12 74. [74.0% 01 0.1 0.0 02 0.2 0.5 US1618 US$1,618 $678.6 [$678. 4601 $4,601. US910 US$910 $46 ($4 4033 $4,033. 36 3. 0. (9 [ (33 (15 (1 [74.0 US161 US$1,61 $678. [$678 $4,601 US91 US$91 $4 ($ 403 $4,033 (3 [74. US16 US$1,6 $678 [$67 $4,60 US9 US$9 $ 40 $4,03 [74 US1 US$1, $67 [$6 $4,6 US$ $4,0 US$1 $6 [$ $4,