Abstract Background Sedatives are essential drugs in every intensive care unit used to ensure the patient's optimal level of comfort. Avoiding conditions of over and under sedation is a challenge in a neonatal intensive care setting. To date, there are no definitions of optimal levels of sedation in neonates. Testing the hypothesis that if a combined use of Neonatal Pain, Agitation and Sedation Scale (N- PASS) and amplitude integrated electroencephalography (aEEG) score might be helpful to distinguish different levels of neonatal sedation and therefore useful in titration of the drugs used. Aim of the Work The primary aim of the present study is to assess Neonatal Pain, Agitation and Sedation Scale (N-PASS) and amplitude integrated electroencephalography (aEEG) in the detection of different levels of neonatal sedation. Patients and Methods This was prospective observational study conducted on 30 full term neonates on mechanical ventilation reciving sedation (midazolam,fentanyl). we divided our patients into two groups (lightly sedated and deeply sedated patients) according to dose of sedation which determined by the expert opinion according to the clinical condition of the patients. all patients were subjected to the following:(demographic data, clinical signs & symptoms, laboratory investigations, N-PASS and aEEG before and after sedation from march 2021 to August 2022 to evaluate N-PASS and aEEG in the detection of different levels of neonatal sedation. Results In our study which was conducted on 30 patients admitted to NICU at Ain shams university hospitals, our patients were of mean gestational age 38.34, all patients presented with respiratory distress, were mechanically ventilated and received sedation (midazolam, fentanyl). we divided our patients into two groups (lightly sedated patients who were 11 patients (36.7%), deeply sedated patients who were 19 patients ( 63.3% ) according to dose of sedation. There was a significant decrease of co2 level in deeply sedated patients, mean co2 after deep sedation 43.36 mmHg while mean co2 after light sedation 51.52 mmHg (p 0.034),and regarding N-PASS significant decrease in N-PASS total score after sedation (p < 0.001 ),and regarding aEEG significant decrease of total burdjalov score after sedation (p < 0.001 ) Conclusion We recommend combining a clinical scoring system such as the N-PASS, with a continuous brain activity monitor such as the aEEG for assessing the level of sedation in neonates.