This retrospective study describes the epidemiological profile of infant mortality in 2000-2002 in 16 counties in Mato Grosso do Sul State, Brazil, and evaluates the preventability of such deaths, using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and the List of Causes of Death Preventable by Interventions in the Setting of the Brazilian Unified National Health System in Children Under Five Years. Perinatal causes accounted for 54.3% of the 1,537 deaths, according to the Mortality Information System; congenital anomalies 14.9%; infectious and parasitic diseases 9.4%; and respiratory disorders 7%. A full 73.1% of deaths were preventable, and most (69.5%) resulted from inadequate prenatal, obstetric, and neonatal care. Additional causes were related to vaccine prevention (0.7%), diagnosis and treatment (10.4%), and health promotion (11.2%). Causes not entirely avoidable accounted for 24.3% of deaths. The findings emphasize the relevance of monitoring adverse maternal-infant conditions and events, particularly to reduce early neonatal mortality (<7 days of life).