Neuropsychiatric syndromes are prevalent in pediatric patients with systemic lupus erythematosus (SLE) and often manifest early in disease course and with significant associated morbidity. Postulated pathogenic mechanisms of peripheral and central nervous system events include vasculopathy, autoantibody effects and systemic inflammation. The pathogenic roles of anti-phospholipid, anti-ribosomal-P and anti-neuronal autoantibodies have been examined in both focal and diffuse adult neuropsychiatric syndromes. Few studies have probed associations between these autoantibodies and pediatric neuropsychiatric SLE (NP-SLE). Retrospective review of a large ethnically diverse pediatric SLE cohort revealed anti-phospholipid, anti-ribosomal P, and anti-neuronal antibodies to be more prevalent than in many adult studies. Rates of anti-phospholipid and anti-ribosomal P antibody positivity were similar to those of other pediatric reports. Association between anti-neuronal antibodies and NP-SLE events appeared statistically significant in this cohort. Prospective inception cohort studies will need to be undertaken to investigate the significance and utility of autoantibody testing in pediatric NP-SLE.