Introduction Clinical estimation of consciousness is the most fundamental and crucial component of neurological examinations for pediatric patients in the pediatric intensive care unit (PICU). The full outline of unresponsiveness (FOUR) Coma Scale assesses four variables: eye response, motor response, brainstem reflexes, and respiratory pattern. A score of 0 represents non-function in each category, whereas a score of 4 indicates normal functioning. The FOUR Coma Scale is easy to apply and is currently the most widely used scale for assessing consciousness, particularly in intubated children. Objectives This study aimed to improve pediatric critical care nurses’ practice in implementing the FOUR Coma Scale. Methods A quasi-experimental research design (pre/post-test design) was employed on a convenience sample composed of 45 male and female nurses who participated in the study and provided direct care for critically ill children at the Medical Pediatric Intensive Care Unit affiliated with the Mansoura University Children's Hospital, Mansoura University, Egypt. All the participants completed the FOUR Coma Scale knowledge and practice assessment questionnaire. Results Majority of the nurses were females and had bachelors’ degrees in nursing (94.6% and 71.1%, respectively). Moray Coma Scale was used to assess level of consciousness (LOC) by more than half the number of nurses (55.6%) in the PICU. All PICU nurses had poor knowledge and practice scores in the pre-intervention phase, and this percentage statistically significantly improved in the post-intervention phase ( P = .001). Conclusion The mean score of nurses’ knowledge and practice on the FOUR Coma Scale significantly improved after the implementation of instructional intervention.