IMPORTANCE: The functional limitations and long-term dependence of children with congenital Zika syndrome (CZS) may lead to changes in maternal occupational roles, which can have a negative impact on mothers' well-being and mental health. OBJECTIVE: To investigate changes in occupational roles and their effects on the mental health of mothers who have a child with CZS. DESIGN: Cross-sectional study. SETTING: Rehabilitation centers of the Brazilian Unified Health System in Alagoas, Northeast Brazil. PARTICIPANTS: Forty mothers of children with CZS. OUTCOMES AND MEASURES: The Role Checklist and the Self-Reporting Questionnaire-20 were used to assess the mothers' involvement in occupational roles and common mental disorders (CMDs), respectively. The relationship between changes in occupational roles and CMDs was analyzed using a logistic regression model. RESULTS: Our study showed that loss of paid work (p = .026) is associated with poor mental health of mothers of children with CZS. CONCLUSIONS AND RELEVANCE: Strengthening public policies to reduce the economic impact of CZS on families, offering multidisciplinary counseling, and implementing psychoeducational strategies for promoting maternal psychological adjustment are needed. WHAT THIS ARTICLE ADDS: The time and money spent by mothers in daily care activities for children with CZS contribute to a reduction in family income and social well-being and have a negative impact on mothers' mental health.