Background: Pain assessment in children who can’t express represent difficult task for good evaluation and effective management; though the present reliable validated pain assessment scales as FLACC scale made the mission easy especially if correlated significantly with extra cortisol secretion. Objective: The present study aimed to assess pain in cognitively impaired children and find its relation to plasma cortisol level as a way for accurate detection and management of pain for a better quality of life. Subjects and Methods: This is a hospital-based case-control study was conducted on 80 children suffering from acute pain (40 children with cognitive impairment and 40 children have a normal cognitive function). 22 were males and 18 were females, the mean of age of cognitive impairment (case) group was 6.7±1.9 years (range (3-12 years) while the mean of age of the control group was 7.8±2.1 years (range (4-12 years). attending the emergency and pediatrics department of Zagazig University Children’s Hospital, Egypt, from March 2015 to December 2015. All studied children were subjected to the following: detailed history taking, careful clinical examination, laboratory investigations including complete blood picture, CRP, serum cortisol level and Face, Legs, Activity, Cry, Consolability pain assessment scale (FLACC scale). Results: There was a significant positive correlation between FLACC scale and serum cortisol level in both case and control. The linear regression for the reliability of serum cortisol level and FLACC scale show that FLACC scale was a good predictor for pain as well as serum cortisol level. Conclusion: FLACC scale could be used as noninvasive easy reliable method for pain assessment and recommended for continuous pain assessment as well as serum cortisol level in children with cognitive impairment. This scale can be used in our practice as initial routine assessment tool to predict pain in cognitively impaired children who are usually exposed to pain and can’t express themselves for better management.