OBJECTIVE: To evaluate the reproducibility and validity of the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) when used in childhood-onset systemic lupus erythematosus (cSLE). METHODS: Forty children with cSLE and 40 matched controls were followed for up to 18 months. Formal neuropsychological testing at baseline was repeated after 18 months of followup; overall cognitive performance and domain-specific cognition (attention, working memory, processing speed, and visuoconstructional ability) were measured and categorized as normal cognition, mild/moderate, or moderate/severe impairment. The 10 Ped-ANAM subtests were completed every 6 months and twice at baseline. Ped-ANAM performance was based on accuracy (AC), mean time to correct response (MNc), throughput, and coefficient of variation of the time required for a correct response (CVc) as a measure of response consistency. RESULTS: Particularly, MNc scores demonstrated moderate to substantial reproducibility (intraclass correlation coefficients 0.47-0.80). Means of select Ped-ANAM scores (MNc, AC, CVc) differed significantly between children with different levels of cognitive performance and allowed for the detection of moderate or severe cognitive impairment with 100% sensitivity and 86% specificity. Six Ped-ANAM subtests significantly correlated with the change in overall cognitive function in cSLE (baseline versus 18 months; Spearman's correlation coefficient >0.4, P < 0.05; n = 24). CONCLUSION: The Ped-ANAM has moderate to substantial reproducibility, criterion and construct validity, and may be responsive to change in cSLE. Additional research is required to confirm the outstanding accuracy of the Ped-ANAM in identifying cognitive impairment, as well as its usefulness in detecting clinically relevant changes in cognition over time.