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The aim of this study was to evaluate the influence of the method of delivery, the level of cord blood lidocaine, and the cortisol concentration on the cord blood natural killer (NK) activity in the full-term healthy newborn. We studied healthy newborns delivered by elective cesarean section without labor under general anesthesia (n = 24), delivered by cesarean section under epidural anesthesia (n = 21), and delivered vaginally with uncomplicated labor (n = 19). The NK cell activity was significantly lower in newborns delivered by cesarean section under epidural anesthesia than it was in the general anesthesia group, while it was similar to the levels found in vaginally delivered newborns. The cortisol concentration was highest in the vaginal delivery group (589.2 ± 200 mmol/l) and lowest in the general anesthesia group (199.2 ± 81.9 mmol/l). The mean serum lidocaine concentration was 414.1 ± 370 μg/l in the epidural anesthesia group and undetectable in the other groups. In conclusion, our data suggest that the cord blood NK activity was significantly influenced by the method of delivery. This effect could be related to anesthetics given to the mother for general or epidural anesthesia or to the endocrine-metabolic variations observed after different degrees of delivery-related stress. The NK cells being a first-line defense mechanism against viral infections, the results of this study suggest an association with the occurrence of early perinatal infections, especially in preterm infants.