Single ventricle surgical palliation with a Glenn surgery universally leads to unintended pulmonary vascular remodeling with pulmonary arteriovenous malformations (PAVMs) and aortopulmonary collaterals (APCs). The pathogenesis of PAVMs and APCs after Glenn is poorly understood, and published literature is limited. Our research team identified increased macrophages in lung biopsies from patients prior chronic Glenn circulation. Most recently we also identified increased lung macrophages and decreased lung lymphocytes in a surgical animal of Glenn circulation. Because lung macrophages and lymphocytes can originate from the bone marrow and circulate in peripheral blood as monocytes and lymphocytes, we hypothesized that peripheral blood samples from patients with chronic Glenn circulation would demonstrate increased monocytes and decreased lymphocytes compared to age-matched controls. We conducted a retrospective cohort study of patients 0-17 years old who underwent cardiac surgery between 1/1/2012 - 1/1/2024. To assess peripheral blood leukocyte counts, we recorded cell counts from pre-operative complete blood counts (CBC) from patients prior to single ventricle palliation (pre-Glenn and pre-Fontan). We also included age-matched control groups (pre-tetralogy of Fallot surgery and pre-atrial septal defect surgery) because normal leukocyte counts are known to change with age. Patient cohorts were identified through an institutional surgical database and CBCs were recorded through manual chart review immediately prior to the date of surgery. We identified a total of 736 pre-surgical CBCs, including 420 single ventricle CBCs (208 28.3% pre-Glenn, 212 28.8% pre-Fontan) and 316 control CBCs (156 21.2% pre-ASD, 160 21.7% pre-TOF). There was no difference in years of age at surgery between our age-matched groups (pre-Glenn 0.35 0.28, 0.45 vs pre-TOF 0.35 0.21, 0.50; p>0.99) (pre-Fontan 3.5 3.0, 4.1 vs pre-ASD 4.3 3.0, 7.1; p=0.19). Compared to their respective age-matched control groups, the pre-Fontan group had increased absolute monocytes (p<0.0001), whereas the pre-Glenn group was not different (p=0.57). Surprisingly, both single ventricle groups had decreased absolute lymphocyte counts (both p<0.0001) and increased absolute neutrophil counts (both p=0.01) compared to their respective control groups. In our single institutional study, chronic Glenn circulation is associated with increased monocytes and decreased lymphocytes in peripheral blood compared to an age-matched control group with an isolated ASD. Further investigation is needed to determine whether peripheral blood leukocyte counts may serve as a biomarker to predict clinical outcomes.