OBJECTIVES. To investigate and compare the leading causes of newborn and infant death in the time of the research periods regarding sex, age, gestational age, body mass, body length, pathological-anatomic diagnosis. STUDY DESIGN. A cross-sectional study. PARTICIPANTS AND METHODS. 185 newborns and infants died in 2015/2016 were involved in the research as well as newborns and infants died in the two-year periods 10, 15 and 20 years ago. The data about the death causes were received from the child’s autopsy reports. If one was not autopsied the data were found in clinical results. The provided data were collected from the archive at the Institute of Pathology and Forensic Medicine of the Clinical Hospital Centre Osijek. RESULTS. The most frequent cause of death of 44 (23.8 %) newborns was a respiratory distress syndrome with a declining trend over the years and for 33 (17.8 %) newborns it was asphyxia. Prematurity as a leading death cause was identified in 16 cases and was at a significantly higher rate in 2015/2016. At the moment of death, 122 (65.9 %) newborns were in the early neonatal period (up to 6 days), 26 (14.1 %) in the late neonatal period, and 36 (19.5 %) in the postnatal period. Out of 8 (4.3 %) newborns diagnosed with sepsis, significantly more were female. Congenital heart defects were the main cause of deaths in the postnatal period (28 – 364 days). CONCLUSION. The leading causes of death in the early neonatal period are the respiratory distress syndrome and asphyxia. In the late neonatal period it is the sepsis, whereas in the postnatal period it is a congenital heart defect. A decrease of respiratory distress syndrome as a leading death cause has been recorded since the examined periods.