Newborn infants, particularly those born prematurely, are prone to develop life-threatening pyogenic infections. Different studies have demonstrated impairment of various aspects of the humoral immunity and the phagocytic activity of neutrophils in newborns. We conducted a comprehensive study evaluating the complement function (CH50 and AP50) and the level of the vast majority of the complement components (Clq, Clr, Cls, C2-C9, FB and properdin) in preterm and full-term newborn infants as compared to adults. Furthermore, we investigated the effect of autologous and heterologous serum on the bactericidal activity of neutrophils, by crossing newborn serum with adult cells and vice versa. Results showed that preterm and full-term newborns have an impaired complement activity as compared to adults (CH50 P<0.05, AP50<0.01) and significantly reduced complement components except for C7, which was found to be normal in full-term infants and in most appropriate-for-gestational age preterm newborns at 34-36 weeks. A statistically significant correlation was found between gestational age and the level of most of the complement components. CH50 and AP50 also showed a positive trend which, however, was not statistically significant. No correlation was found between birthweight and complement activity or complement component levels. The neutrophil bactericidal activity of full-term newborns was about one-third that of adults (P<0.001). Adult serum improved the bactericidal activity of newborn neutrophils by 93%, indicating a considerable neonatal humoral defect. Conversely, neonatal serum blunted the adult bactericidal activity by 86%. Our results support the fact that both humoral and phagocytic functions in newborn infants are impaired, which may possibly account for their increased tendency to develop severe pyogenic infections.