BACKGROUND: Bacterial Sepsis is a serious medical problem affecting children with Congenital Heart Disease (CHD). The pattern and factors predicting outcome of bacterial sepsis have not been studied in Africa. The study aimed to describe the pattern and outcome of bacterial sepsis among children with CHD in Tikur Anbessa Specialized Hospital (TASH).METHODS: A cross-sectional study was carried out among children with CHD and sepsis at TASH between May 2017 and July 2020. Structured questionnaires were used for data collection. Statistical significance was set at P value < 0.05, and multivariable logistic regression was used to determine predictors.RESULTS: This study included 384 CHD children with sepsis.  Proportion of culture proven bacterial sepsis was 17.1 % (66) (95% CI: 13.6- 21.3).  Coagulase negative staphylococcus aureus 7% (27), Staphylococcus aureus 4.4% (17) and Actinobacteria 1.8% (7) were the common isolated bacteriological agents. Death was documented in 25% (96) of study subjects. Down syndrome subjects were 2.4 times [aOR=2.416 (95%CI: 1.367-4.264)] more likely to die from sepsis. Those with associated comorbidities (Apert syndrome, Cerebral palsy, Chiari 2 malformation, Patau syndrome, Noonan syndrome, Congenital Rubella, Portal vein thrombosis, HIV, Scoliosis and VACTERL association) were 4.4 times more likely to die from sepsis [aOR=4.418 (95%CI: 1.617- 12.072)].CONCLUSION: Bacterial sepsis is a common problem among children with CHD. Gram positive bacteria were common causes. Down syndrome and other co morbidities predicted bacterial sepsis mortality. Blood culture and sensitivity tests are recommended to halt the high mortality seen in Down syndrome or those with co morbidities.KEYWORDS: Congenital heart disease, bacterial sepsis, Down syndrome, Ethiopia