Neuropsychiatric involvement in SLE (NP-SLE) may not be picked up by routine neuroimaging procedures like computerized tomography (CT) or magnetic resonance imaging (MRI). We prospectively studied the role of single photon emission computerized tomography (SPECT) and magnetic resonance spectroscopy (MRS) in detection of NP-SLE in 20 patients with lupus (10 with clinical NP involvement and 10 without) and 9 healthy controls. MRI abnormalities were seen in 5/10 patients with NP-SLE while the MRI was normal in all the lupus patients without clinical NP involvement. Perfusion defects on SPECT were seen in as many as 8/10 patients with NP-SLE while only 1/10 lupus patients without clinical NP involvement and none of the healthy controls demonstrated perfusion defects. MRS revealed abnormal metabolite ratios in all patients with NP-SLE and as many as 8 lupus patients without clinical NP features. Normal metabolite ratios were observed in healthy controls. SPECT and MRS can help detect changes not evident on MRI and may serve as useful supplements to existing neuroimaging techniques in the diagnosis of NP-SLE. The precise significance of alterations in regional cerebral blood flow on SPECT and neurometabolite ratios on MRS needs larger, longitudinal studies.