Background: Wee care is an essential element for caring of preterm neonates in intensive care units. It decreases mismatching between intrauterine and extra uterine life which improves physical growth and neuro-behavior stability of preterm neonates. Aim: is to determine the effect of wee care on physical growth and behavioral responses of preterm neonates. Subjects and method: Design: A quasi experimental design was used to accomplish this study. Setting: The study was conducted at the Neonatal Intensive Care Unit at Alexandria University Children's Hospital at Smouha. Subjects: A convenient sample of 60 preterm neonates were selected to perform the current study. Tools: Three tools were used for data collection, Tool I: Characteristics and clinical data of preterm neonates' record, Tool II: Preterm neonates physiological parameters and physical growth record. Tool III: Assessment of Preterm Infants` Behavior Scale (APIB). Results: the result of the current study revealed that the preterm neonates of the study group have more means of weight gain than the control group with statistically significant differences. Statistically significant differences were found regarding total score of behavior responses of preterm neonates between the study and control groups in day 1 and day 21. The study group had higher mean of oxygen saturation and lower means of respiratory rate within normal range compared to the control groups Conclusion: The study concluded that application of wee care for preterm neonates in neonatal intensive care unit enhance weight gain, improve autonomic visceral responses, and improve behavioral organization. Recommendations: Application of Wee care for preterm neonates should be included in the updated policy of neonatal intensive care units. It should be incorporated as a part of the routine care for preterm neonates.