Mothers caring for their children with leukemia during COVID-19 pandemic are facing several barriers, however nurses play a fundamental role in caring for children with leukemia. Aim of the study was to assess barriers faced by mothers caring for their children with leukemia during COVID-19 pandemic. Setting: This study was carried out in Pediatric Oncology Department at Benha Specialized Pediatric Hospital affiliated to Specialized Medical Centers Secretariat. Design: A descriptive quantitative study design was utilized. Subjects: A purposive sample of mothers and their children aged from 5 to 16 years old with leukemia. Tools of data collection: Tool I: A structured interviewing questionnaire used to assess; Personal characteristics of the studied mothers, personal characteristics of the studied children and mother’s knowledge about childhood leukemia and COVID-19. Tool II: Barriers faced by mothers caring for their children with leukemia during COVID-19 pandemic. Results: Slightly less than two fifth of studied mothers (39.5%) had poor knowledge about childhood leukemia. While, more than one third (34.1%) of them had average knowledge. Slightly less than three fifth of studied mothers (59.4%) had poor knowledge about COVID-19. While, less than fifth (15.4%) of them had good knowledge. The most barriers faced by mothers is social barriers constituting about more than two thirds (71.4%). While the less barriers faced by mothers is related to hospital barriers constituting about more than half (50.7%). Conclusion: There is a positive relation between barriers faced by mothers caring for their children with leukemia during COVID-19 pandemic and their (personal characteristics & knowledge regarding COVID-19 pandemic). Recommendation: Designing and implementing an educational program for mothers about COVID-19, its effects on children with leukemia and COVID-19 vaccination for children with leukemia