An institution-based surveillance and nested case-control study was conducted in Natal, Northeastern Brazil to estimate the level and determinants of early neonatal mortality. The early neonatal mortality rate was 25.5 per 1000 live-births, 75% of early neonatal deaths were premature low birthweight infants, and the mortality rates were 591 and 318 per 1000 respectively, for preterm small for gestational age (PT-SGA) and preterm appropriate for gestational age (PT-AGA) infants. Mortality was 50 per 1000 for term low birthweight, and 8.6 for term normal birthweight AGA infants. In addition to prematurity and low birthweight, the main risk factors associated with early neonatal death were maternal smoking, complications during pregnancy or intrapartum, and inadequate antenatal care. The associations were weaker for prepregnancy factors such as single marital status or low maternal body weight, and no significant associations were observed with socioeconomic status. These findings suggest that in this population, efforts to reduce early neonatal death should focus on improved maternal care and the prevention of prematurity.