A recent publication in The Lancet by Cordeiro and colleagues reported levels of IgM for Zika (ZIKV) and dengue (DENV) viruses in serum and cerebrospinal fluid (CSF) of 31 infants born with microcephaly in Brazil. 1 Their study suggests higher titers in CSF relative to serum in individual neonates, but no quantitative comparisons were reported. In this short report, the differences in antibody titers are quantified and compared between sample sources; across sampling periods; and between sample sources within individual neonates to more comprehensively understand these data to inform serological surveillance. These are statistically significant differences in ZIKV titers between CSF and serum samples, (in contrast to DENV titers), and these ZIKV titer levels remain elevated across sampling dates, whereas the titer in serum trends downward by sampling date. In multivariate models, ZIKV titer in CSF samples is independent of titer in serum, and of DENV antibodies in both CSF and serum. These findings quantify the compartmentalization of ZIKV antigens across the blood-brain barrier, and suggest complex interplay between ZIKV and cross-reacting DENV antigens in congenital/neonatal infections.