Monitoring serum immunoglobulin G (IgG) levels in pediatric oncology patients and treating subtherapeutic levels with intravenous immunoglobulin (IVIG) may prevent infections; however, evidence is limited. This retrospective study assessed pediatric acute lymphoblastic leukemia patients diagnosed 2006 to 2011 to evaluate if monitoring/supplementing IgG would reduce febrile illnesses during maintenance chemotherapy. A subject was categorized as "ever IgG monitored" if they had ≥1 IgG levels checked and their risk days were stratified into not IgG monitored days and IgG monitored days. IgG monitored days were further stratified into IgG monitored with IVIG supplementation, monitored with no IVIG supplementation (IgG level >500 mg/dL) and monitored with no IVIG supplementation days (IgG level <500 mg/dL). Generalized linear mixed effects poisson models were used to compare events (febrile episode, positive blood culture, and febrile upper respiratory infection rates among these groups. In 136 patients, the febrile episode rate was higher in the ever IgG monitored cohort than the never monitored cohort (5.26 vs. 3.78 episodes/1000 d). Among monitored patients, IVIG monitoring and supplementation did not significantly impact the febrile episode, febrile upper respiratory infection, or the positive blood culture rates. These data suggest that monitoring/supplementing low IgG is not indicated for infection prophylaxis in acute lymphoblastic leukemia patients during maintenance chemotherapy.