Background: Pulse oximetry device is widely used nowadays in both Neonatal Intensive Care Unit (NICU) and Pediatric Intensive Care Unit (PICU) so assessment of its accuracy is very important as a rapid life saving decisions is taken depending upon its reading. Objectives: The primary objective of this study was to evaluate the accuracy of simultaneous samples of SpO2 compared with SaO2 obtained by CO-oximetry throughout a range of SpO2 values. Other objectives were to identify factors that may affect the bias of SpO2 compared with SaO2 such as age, sex, Hb level, PaO2 level and perfusion state. Patients and Methods: This study was a cross section observational study. It was carried out at El-Mabarrah hospital in Tanta city. It included Two hundred patients of different pediatric age groups who were admitted to Neonatal Intensive Care Unit (NICU) and pediatric intensive care unit (PICU) from February to December 2015. Patients aged from first day to16 years old and have any indication of NICU or PICU admission were included in our study while patients with major congenital malformations or have traumatic or surgical causes of admission where excluded. They were studied by comparison between SpO2 and SaO2 values. Factors that may affect SpO2 such as age, sex, Hb level, PaO2 level and perfusion state and correlation between SpO2 and ABG findings such as PaO2, pH, PCO2, HCO3 were assessed. Confidentiality of data, approval of research ethics committee and informed written consent from parents were obtained before conducting the study. Results: The study revealed that; there was a statistically significant difference between SpO2 and SaO2 in the whole entire range of SpO2 and in each category of SpO2 in both studied groups. There was no effect of age and sex on the accuracy of pulse oximetry. On the other hand it was affected by Hb level(p=<0.05), low PaO2 level(p ≤ 0.001), and prolonged capillary refilling time (p ≤ 0.001).Also there was a statistically significant positive correlation between PaO2 and SpO2 but no statistically significant correlation between SpO2 and pH, PCO2, HCO3. Conclusion: The pulse oximeter remains a valuable tool in the care of intensive care patients, but an awareness of its limitations is an important component of enhancing the quality of care. In condition with oxygen saturation (SpO­₂<80%) and in critical status, SpO2 is not sufficiently accurate to replace SaO2 measured by arterial blood gases analyzer. Better pulse oximetry algorithms are needed for accurate assessment of children with saturations in the hypoxemic range.