Systemic lupus erythematosus with neuropsychiatric involvement (NPSLE) can be diagnosed clinically, but there is no definite serological biomarker established. The objectives of this study were to evaluate the neuropsychiatric involvement in systemic lupus erythematosus (SLE) patients and to detect the autoantibodies associated with them. Sixty NPSLE patients along with sixty SLE patients without neuropsychiatric involvement from Maharashtra, India, were included. All patients were clinically diagnosed using the American College of Rheumatology criteria. Disease activity was assessed using the systemic lupus erythematosus disease activity index. Antinuclear antibodies (ANA), anti-dsDNA, anti-neuronal antibodies were detected by indirect immunofluorescence test. Anti-ribosomal antibodies (anti-Rib-P) were tested by ELISA. NPSLE was diagnosed in age group ranging between 10 and 20 years compared with SLE patients without neuropsychiatric involvement (21-30 years). The most frequent symptoms were psychosis (75%), followed by seizures (58%), lupus headache (40%), cognitive dysfunction (36%), mood disorder (30%), cerebrovascular disease (20%), and anxiety (18%). ANA were present in all. The prevalence of anti-Rib-P was 26.6% in NPSLE and 16.6% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found in 56.7% in NPSLE and 43.4% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found to be highest in the patients of psychosis (66.6%) followed by central nerve system disease (63.63 %) and seizures (56.25%). There was an early onset of neuropsychiatric involvement. Anti-Rib-P antibodies as well as anti-neuronal antibodies did not show statistically significant correlation with neuropsychiatric manifestations in NPSLE patients.