BACKGROUND: The mechanism of cognitive dysfunction in systemic lupus erythematosus (SLE) is still not fully understood. Even though many SLE patients present some neurological dysfunction, including various cognitive deficits, neither a specific pattern of cognitive dysfunction nor specific structural changes associated with cognitive impairment in SLE patients have been established. Moreover, although prevalent and bothersome, cognitive deficits have not been included in the most recent SLE diagnostic criteria. PURPOSE: The aim of this study was to determine the relationship between the presence of white matter lesions (WMLs) and cognitive dysfunction in patients diagnosed with SLE. RESEARCH DESIGN: 33 SLE patients underwent 3 T brain magnetic resonance imagining (MRI) and an extensive battery of psychological tests, including Automated Neuropsychological Assessment Metrics (ANAM) and the standard pen and paper neuropsychological tests. Patients were stratified into two groups based on the presence ( RESULTS AND CONCLUSIONS: Significant deficits in cognitive functions were observed. Patients with WMLs showed deficits in attention and executive functions, as well as memory deficits in comparison to the group without WMLs. As measured with: STROOP Test (executive function), Color Trail Test (CTT) (attention), Californian Verbal Learning Test (CVLT) (memory), and from ANAM tests with: Procedural Reaction Time (PRT) (attention), Code Substitution Delayed (CS_D) (memory), Spatial Processing (SP) (visuospatial functions), Tower Puzzle (TP) (executive functions), 2 Choice Reaction Time (2CHRT) (attention), Running Memory CPT (RM CPT) (memory), Matching Grids (Mat GR) (visuospatial functions), Go/No _Go inhibition (Go/No_Go Go) (executive functions). Additionally, we analyzed structural volumetric measures derived from a comprehensive segmentation pipeline recon-all using Freesurfer 5.3. Significant differences were identified for the following structures' volumes: right choroid plexus, left choroid plexus, right lateral ventricle. All these structures had a greater volume in patients with WMLs.