The diagnosis and pathology of neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging. Herein, we used multimodal imaging to assess anatomical and functional changes in brains of SLE patients instead of a single MRI approach generally used in previous studies. Twenty-two NPSLE patients, 21 non-NPSLE patients and 20 healthy controls (HCs) underwent 3.0 T MRI with multivoxel magnetic resonance spectroscopy, T1-weighted volumetric images for voxel based morphometry (VBM) and diffusional kurtosis imaging (DKI) scans. While there were findings in other basal ganglia regions, the most consistent findings were observed in the posterior cingulate gyrus (PCG). The reduction of multiple metabolite concentration was observed in the PCG in the two patient groups, and the NPSLE patients were more prominent. The two patient groups displayed lower diffusional kurtosis (MK) values in the bilateral PCG compared with HCs (p < 0.01) as assessed by DKI. Grey matter reduction in the PCG was observed in the NPSLE group using VBM. Positive correlations among cognitive function scores and imaging metrics in bilateral PCG were detected. Multimodal imaging is useful for evaluating SLE subjects and potentially determining disease pathology. Impairments of cognitive function in SLE patients may be interpreted by metabolic and microstructural changes in the PCG.