Background: Postnatal sepsis is one of the problems that threaten the lives of mothers, although it can be avoided by taking the necessary precautions. The nurse and midwife represent the cornerstone in preventing and treating infections during the postpartum period. Study Design: This semi-experimental study Sudan, River Nile state to evaluate the effectiveness of designed guidelines for midwives regarding postnatal sepsis management, during the period March 2017 to January 2020. Sample Size: The study included 73 midwives. Data Collection Tools: Data were collected in two stages using a standard questionnaire and a list of observations before and after the training program. Data Analysis: The data were analyzed by a computer software program (SPPS) version 23. The result showed that the level of knowledge is improved significantly after guidelines interventions, where Nursing assessment and management 20.8% had bad practice while this is improved 82.6% very good practice. only12.5% of respondents scored very good Skills full of maintaining vulval hygiene and Maternal hygiene, which change to 100% very good score after interventions. concerning counseling regarding prevention and management 29.2% considered as bad practice changed to 91.3% Very Good Practice after interventions of guidelines. Conclusion: The study concluded that the majority of nurses midwives had high knowledge score in the post-test compared with pre-test and they demonstrated good practice which indicated that the postpartum infection management training guidelines program was effective.