Although the transfusion of blood products is common practice, its effects on the immune system have not been adequately studied. A prospective cohort study was conducted in critically ill children followed up until their death, transfer or discharge to establish an association between red blood cell transfusions (RBCTs) and nosocomial infections. A nosocomial infection was considered to be post-transfusional if it occurred within 14 days after RBCT. A total of 162 children were included in the study, 35 (21.6%) had a nosocomial infection, and 49 (30.2%) received a RBCT. Among those with a nosocomial infection, a RBCT was more common (48.5% versus 14.9%, OR: 5.4, 95% CI: 2.4-12.6, p < 0.0001) and mortality rate was higher (45.7% versus 10.2%, OR: 7.4, 95% CI: 3.1-18.2, p < 0.0001). The binary logistic regression showed that RBCT was independently associated with nosocomial infections (OR: 4.2, 95% CI: 2.1-20.2, p=0.049). Conclusion: RBCT was associated with increased risk for nosocomial infections.