Objective: The study aims to estimate catastrophic health expenditures associated with the diagnosis and follow-up treatment of Congenital Zika Syndrome (CZS) in children affected during the 2015-2016 epidemic in Brazil. Catastrophic health expenditures are defined as health spending that exceeds a predefined proportion of the household’s total expenditures, exposing family members to financial vulnerability. Methods: Ninety-six interviews were held in the cities of Fortaleza and Rio de Janeiro in a convenience sample, using a questionnaire on sociodemographic characteristics and private household expenditures associated with the syndrome, which also allowed estimating catastrophic expenditures resulting from care for CZS. Results: Most of the mothers interviewed in the study were brown, under 34 years of age, unemployed, and reported a monthly family income of two minimum wages or less. Spending on medicines accounted for 77.6% of the medical expenditures, while transportation and food were the main components of nonmedical expenditures, accounting for 79% of this total. The affected households were largely low-income and suffered catastrophic expenditures due to the disease. Considering the family income metric, in 41.7% of the households, expenses with the child’s disease exceeded 10% of the household income. Conclusion: Public policies should consider the financial and healthcare needs of these families to ensure adequate support for individuals affected by CZS.