Background: Breastfeeding is the best choice for preterm infant feeding. Supporting mothers during Covid-19 requires innovative electronic methods for delivery of health education and protective measures for safe breastfeeding. Aim of the study to evaluate the effect of an electronic-based instruction guide for supporting mothers regarding safe breastfeeding of their preterm infants during Covid-19 pandemic based on mothers' breastfeeding perception, self-efficacy, safety measures practices, breastfeeding technique, and attitude. Design: A quasi-experimental research design was conducted on 100 participating mothers of preterm infants. Settings: The study was carried out at neonatal care unit and breastfeeding clinic in obstetric and gynecological hospital affiliated to Ain Shams University. Tools: Data was collected using 1) An Interview Questionnaire Format to assess mothers' demographic characteristics and their breastfeeding perception; 2) Breastfeeding Self-Efficacy Scale-Short Form; 3) Observational checklist of Safety Measures Practices of Breastfeeding, 4) The Bristol Breastfeeding Assessment Tool and 5) The Iowa Infant Feeding Attitude Scale. The Results highlighted most of mothers were improved their mean scores of breastfeeding perception, self-efficacy, safety measures practices, breastfeeding technique, and attitude with statistically significant differences pre, post applying electronic-based instruction guide (t-test =34.887, 17.388, 42.52, 4.172 and 17.886 respectively at P- value= <0.001). The results also revealed a positive correlation between mother's self-efficacy with their attitude post applying electronic-based instruction guide (r = 0.642 at P- value= <0. 01). Conclusion: the electronic-based instruction guide had a significant positive change in mothers' breastfeeding perception, self-efficacy, safety measures practices, breastfeeding technique, and attitude regarding safe breastfeeding of their preterm infants during Covid-19 pandemic. Recommendation: Adopting electronic-based instruction as a method for supporting breastfeeding mothers of preterm infants during Covid-19.