<ns3:p><ns3:bold>Background</ns3:bold>:<ns3:bold> </ns3:bold>Children with congenital Zika syndrome (CZS) have a wide range of additional healthcare needs. This study aimed to estimate the direct costs of CZS from the health provider and family perspectives, and the indirect costs for families, in two Brazilian states: Rio de Janeiro and Pernambuco.</ns3:p><ns3:p> <ns3:bold>Methods: </ns3:bold>A case-control study was undertaken between May 2017-January 2018 recruiting 174 cases with severe CZS, 41 with mild/moderate CZS and 269 children with no CZS, across the two sites, from existing studies. The primary caregiver was interviewed using a structured questionnaire to collect information on healthcare use and costs incurred during the previous 12 months. In Rio de Janeiro, health care utilization data was also extracted from electronic medical records. We estimated direct and indirect costs incurred as a result of CZS from the perspective of the health system and families.</ns3:p><ns3:p> </ns3:p><ns3:p> <ns3:bold>Results: </ns3:bold>Children with CZS accessed more healthcare facilities and reported longer travel and waiting times than children unaffected by CZS. Total costs from the health provider perspective of outpatient visits, were highest for children with severe CZS (U$1,411) followed by children with mild/moderate CZS (U$264) and children without CZS (U$107). This pattern was apparent for direct costs incurred by families, while median indirect costs were low. Families of children with CZS reported high levels of catastrophic expenditures; Expenses incurred by families to meet their child’s needs as a proportion of household income was 30% (IQR=14%-67%, p&lt;0.01) for children with severe CZS, 11% (IQR=4%-33%, p&lt;0.01) for mild/moderate CZS, and 1% (IQR=0%-8%) for controls. Costs incurred by families were generally higher in Rio de Janeiro than Pernambuco.</ns3:p><ns3:p> <ns3:bold>Conclusions</ns3:bold>: Families of children affected by CZS in Brazil may need additional public health resources and social benefits to protect them from incurring catastrophic expenses while meeting the needs of their children.</ns3:p>