Children with congenital heart disease undergoing cardiac surgery are at risk for laboratory-confirmed bloodstream infections (LCBIs). These infections can lead to morbidity, mortality, and increased health care costs. The role of mucosal barrier injury in causing LCBIs is unknown. To describe characteristics of LCBIs in patients admitted to cardiac intensive care and step-down units and to assess frequencies of National Healthcare Safety Network infection types and associations with organism classification, patient clinical factors, and infection outcomes. A retrospective cohort analysis using manual electronic medical record data abstraction included children with congenital heart disease who developed an LCBI while receiving inpatient cardiac care between August 2011 and November 2018 at one institution. Demographic, clinical, laboratory, and outcome variables were collected and analyzed with descriptive and inferential statistics. Eighty-seven patients with congenital heart disease developed 103 LCBIs during the study time frame. The most common causative microorganisms were gram-positive bacteria, including Enterococcus faecalis and Staphylococcus epidermidis. Sixty-three percent of causative organisms were characterized as originating from mucosal barrier injury, although no infections met National Healthcare Safety Network criteria for mucosal barrier injury LCBIs. Translocation of bacteria through injured gut mucosa may cause bloodstream infections in children with congenital heart disease. Further investigation is warranted to understand microbiome changes that adversely select pathogenic gut organisms. Preventive care to maintain intact gut function and a healthy microbiome should be explored for this patient population.