Upper respiratory tract infections are common diseases that are mostly caused by viral infections. Although antibiotics are medications used for the treatment of bacterial infections, antibiotics are the most commonly prescribed and abused drugs for upper respiratory tract infections globally, which can lead to bacterial resistance. The aim of this study: was to assess mothers' knowledge and reported practices regarding antibiotics use to their preschool children with upper respiratory tract infections. Descriptive correlational design was utilized to achieve the aim of the study. Setting: The study was conducted at outpatient pediatric clinic in Bir El-Abd central hospital, North Sinai. Sample: Included 220 mothers who have preschool children suffering from upper respiratory tract infections by using none probability purposive sampling method. Data was collected using structured interviewed questionnaire. Results: Less than half of the studied mothers have unsatisfactory level of knowledge and less than two thirds of the studied mothers have unsatisfactory level of reported practices regarding antibiotics use to their preschool children suffering from upper respiratory tract infections. Conclusions: There was a statistically significant positive correlation between mothers' knowledge and their reported practices. Recommendations: Educational workshops were required for mothers to enhance their knowledge and practices regarding antibiotics use to their children.