The aim of the study was to find structural brain changes in systemic lupus erythe-matosus patients without major neuropsychiatric manifestations [non-neuropsychiatricsystemic lupus erythematosus (non-NPSLE)] using quantitative magnetic resonanceimaging (MRI) and possible associations with clinical characteristics. 89 non-NPSLEpatients with normal conventional MRI and 84 healthy controls (HCs) were recruited. Thewhole brain gray matter volume (GMV) and white matter volume (WMV) were calculatedfor each individual. We found obvious GMV and WMV reduction in the systemic lupuserythematosus (SLE) group compared with HCs. Female patients showed significantreduction of GMV and WMV compared with male patients. Patients treated with immu-nosuppressive agents (ISA) showed less WMV reduction than those without. Cognitiveimpairment was the most common subclinical neuropsychiatric manifestation and hada prevalence of 46.1%. Association between WMV reduction with cognitive impairmentwas found. Thus, we concluded that structural brain atrophy could happen even beforeoccurrence of obvious neuropsychiatric signs and symptoms and was associated withsubclinical symptoms such as cognitive impairment. ISA treatment might have a protec-tive effect on the brain atrophy. Early treatment might prevent the progressive damageto the brain. More studies are needed to fully understand the complicated underlyingmechanisms of brain atrophy in SLE.