OBJECTIVE To determine whether red blood cell transfusion is similarly associated with nosocomial infections in pediatric intensive care unit patients and whether reduced lymphocyte numbers is a possible mechanism. In adult studies, red blood cell transfusions are associated with nosocomial infections. METHODS Historical cohort study. METHODS Single-center, mixed medical-surgical, closed pediatric intensive care unit of a tertiary university-affiliated children's hospital. METHODS All patients < or = 18 yrs old admitted to the pediatric intensive care unit during a 6-month period from January 1 to July 3, 2005. METHODS None. RESULTS Nosocomial infections (respiratory, urinary tract, and bloodstream infections) were the primary outcome measure and were defined as post transfusion if occurring within 14 days after red blood cell transfusion. Of the 209 subjects enrolled, 32 (15%) acquired nosocomial infections and 45 (22%) received red blood cell transfusions. Patients with versus without nosocomial infections had received red blood cell transfusions significantly more often (odds ratio, 18.0; 95% confidence interval, 7.6-45.9; p < .001). In a dose-dependence analysis, we found that patients receiving > or = 3 red blood cell transfusions had a similar prevalence of nosocomial infections compared with those receiving one to two red blood cell transfusions (61% vs. 44%, p = .365), but greater mortality (22% vs. 0%, p = .04). In a multiple logistic regression analysis controlling for gender, age, pediatric intensive care unit length of stay, presence of an invasive catheter, mechanical ventilation, and surgery, red blood cell transfusion remained independently associated with risk of nosocomial infection (odds ratio, 3.73; 95% confidence interval, 1.19-11.85, p = .023). Transfused subjects had lower absolute lymphocyte counts compared with nontransfused subjects (1605 vs. 2054/microL, p = .041), but similar total white blood cell counts (10.4 vs. 11.4 x 10/microL, p = .52). CONCLUSIONS Red blood cell transfusion in pediatric intensive care unit patients is associated with an increased risk of nosocomial infections.