Dissertation (MSc Midwifery)Background: Neonatal sepsis is the clinical infection categorized as early and lateonset that is a public health challenge all over the world. Number of factors; Premature rupture of membrane >18hours, repeated per vaginal examination, Prolonged/obstructed labor, antenatal care attendances have been associated with neonatal sepsis. Despite of all national interventions, Tabora Region is still the region with a high morbidity of neonatal sepsis at the western zone by 6.8%. Risk factors are still obscure. The aim of this study was to assess predictors associated with neonatal sepsis at Kitete Hospital. Methods: Quantitative and hospital based cross-sectional study was conducted at Kitete hospital which was selected purposively due to high number of neonatal morbidities 6.8%. A total number of 328 (100%) response rates of post delivery mothers and their neonates were selected to participate into the study by using a simple random sampling with lottery method. Blood culture and sensitivity test was done to confirm neonatal sepsis, as well as questionnaires were used to collect data. SPSS version 20 was used for data analysis and descriptive and inferential statistics were employed. Results: The prevalence of neonatal sepsis in Tabora region is 23.2%. Predictors which were associated with neonatal sepsis were antenatal care < 4 visits (AOR 4.297; 95% CI: 2.163, 8.534), more than four per vagina examination (AOR 2.735; 95% CI: 1.111, 6.734), premature rupture of membrane > 18 hrs during labor (AOR: 2.735; 95% CI: 1.235, 6.911) and prolonged/obstructed labour (AOR: 3.517; 95% CI: 1.521, 8.113) Neonatal risk factors and knowledge on infection prevention did not show association with neonatal sepsis. Conclusion: Neonatal sepsis is still a public health challenge in Tabora region with the prevalence of 23.2%. Important factors noted to contribute neonatal sepsis were Antenatal care attendance less than 4 visits, prolonged labour/obstructed labour, premature rupture of membrane >18 hours during labour and per vagina examination for more than four examinations.