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Background: The clinical manifestations of microcephaly/congenital Zika syndrome (microcephaly/CZS) have harmful consequences on the child's health, increasing vulnerability to childhood morbidity and mortality. This study analyzes the case fatality rate and child–maternal characteristics of cases and deaths related to microcephaly/CZS in Brazil, 2015–2017. Methods: Population-based study developed by linkage of three information systems. We estimate frequencies of cases, deaths, case fatality rate related to microcephaly/CZS according to child and maternal characteristics and causes of death. Multivariate logistic regression models were applied. Results: The microcephaly/CZS case fatality rate was 10% (95% CI 9.2–10.7). Death related to microcephaly/CZS was associated to moderate (OR = 2.15; 95% CI 1.63–2.83), and very low birth weight (OR = 3.77; 95% CI 2.20–6.46); late preterm births (OR = 1.65; 95% CI 1.21–2.23), Apgar < 7 at 1st (OR = 5.98; 95% CI 4.46–8.02) and 5th minutes (OR = 4.13; 95% CI 2.78–6.13), among others. Conclusions: A high microcephaly/CZS case fatality rate and important factors associated with deaths related to this syndrome were observed. These results can alert health teams to these problems and increase awareness about the factors that may be associated with worse outcomes. [ABSTRACT FROM AUTHOR]