Background: Infection with the Herpes Simplex Viruses (HSV) type 1 and 2 is fairly frequent.  While HSV-1 infections have traditionally been linked with oral lesions and HSV-2 infections with genital illness, both virus serotypes can infect either region.  The purpose of this study was to assess how a blended learning program affected parents' knowledge of how to care for children with herpes simplex. Research design: A quasi-experimental design (Pretest/Post-test quasi-experimental design) was used in this study. Setting: This study was conducted at the Out-Patient Pediatric Clinic at Beni-Suef University Hospital. Subjects: The study subjects consisted of a purposive sample of 100 parents having children diagnosed with herpes simplex. Tools of data collection: Two tools were used: Tool (1) A structured questionnaire; part (1) Demographic data of parents, part (2) Knowledge test (Pre-Post). Tool (2) A self-reported practice (pre/post-tests). Results: It showed that parents' knowledge and practice regarding caring for children with herpes simplex have improved in the post-test program compared with the pre-test program, with a highly statistically significant difference. Conclusion: Blended learning program regarding caring for children with herpes simplex had a significant positive effect in improving parents' knowledge and practice towards caring for children with herpes simplex. Recommendation: Providing continuous education and training for parents regarding caring for children with herpes simplex.