Introduction: Hypoxemia is the major cause of neonatal morbidity and mortality. The study aims to determine the influence of birth weight, Apgar score, gestation age, body mass index and hemoglobin of mother on levels of SpO2 in healthy newborns born vaginally and through cesarean section. Methods: A hospital Based, observational study conducted in Department of Pediatrics, Universal College of Medical Sciences-Teaching Hospital, Bhairahawa, Lumbini, Nepal; on 49 vaginal and 49 cesarean deliveries with Apgar Score ≥ 6. SpO2 was estimated by pulse oximeter post-ductally between 1 to 30 minutes of birth. The observed SpO2 values were correlated with neonatal and maternal factors. Results: Vaginal and Cesarean deliveries SpO2 were comparable for birth weight, gestational age, Apgar score of neonates, body mass index and hemoglobin of the mother. Birth weight in vaginally delivered babies and Apgar score in cesarean births showed significant change in SpO2 (P<0.05). At all points of time the SpO2 values were higher in neonates, born by cesarean than those born out of spontaneous vaginal deliveries (P<0.001). Conclusions: SpO2 levels in neonates born through cesarean section were higher in comparison to thoseborn by vaginal route. Birth weight and Apgar score had correlation with SpO2 in vaginal and cesarean births, respectively. Keywords: Apgar score; birth weight; newborn; pulse oximeter; SpO2.