Background: Neonatal sepsis considers as a serious health issue throughout the world as it is a major neonatal problem in developed and developing countries.Early diagnosis and proper management of sepsisamong neonates can preventpermanent disability and deathrate in neonates. The vital role of nurses about sepsis and their ability to detect the clinical features of the neonatal sepsis, which helps to make paramount importance for early diagnosis and prompt management. Objectives: To find out the level of knowledge regarding neonatal sepsis among nursing students in selected school of Nursing, Bhubaneswar.To evaluate the effect of self-instructionalmodule on neonatal sepsis among nursing students.To evaluate the association between level of knowledge regarding neonatalsepsis with their selected demographic variables among nursing students. Methods: The present study was carried out as pre-experimental design at selected School of Nursing Bhubaneswar, Odisha. A total 120 number of nursing students were selected by purposing sampling technique. Validity was checked by experts and reliability test wasdone. Descriptive and inferential statistics were used to analyze the data. Results: The result shows, in pretest, students (66%) were having poor level of knowledge regarding neonatal sepsis where as in posttest after implication of intervention teaching module, students (68%) were having very good knowledge. Likewise, in pretest 35% were having less knowledge in the area of clinical manifestation and diagnostic evaluation, but in posttest it was increased to 86%. And there was no significant association found with sociodemographic variables. Conclusion: Study concluded that the self-instructional module was effective in increasing the level of knowledge amongnursing students. Nursing personnel can also utilize this module at educational setting as well as clinical setting in improving knowledge of nursing students.