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To determine the temporal relationship between the transfusion of RBCs and the subsequent development of delirium in a cohort of critically ill children.Nested retrospective cohort study within prospective cohort study.Urban academic tertiary care PICU.All consecutive admissions from September 2014 through August 2015.Children were screened twice daily for delirium during their PICU admission.Among 1,547 independent admissions screened for delirium, 166 (10.7%) were transfused RBCs. Children who were transfused RBCs were more than twice as likely to be delirious during their admission compared with children who were never transfused, after controlling for known predictors of delirium development (adjusted odds ratio, 2.16; 95% CI, 1.38–3.37; p = 0.001). Among transfused children, a temporal relationship was observed between receipt of RBCs and the subsequent development of delirium. For each additional 10 mL/kg of RBCs transfused, the recipients were 90% more likely to develop delirium or coma in the 72 hours following the transfusion, after controlling for confounders (adjusted odds ratio, 1.90; 95% CI, 1.14–3.17; p = 0.01). Anemia (represented by nadir hemoglobin prior to transfusion) was not associated with delirium development.In this cohort of critically ill children, there is an independent association between the receipt of an RBC transfusion and the subsequent development of delirium. Further prospective studies are warranted to replicate this finding and investigate possible pathophysiologic mechanisms for this association.