Introduction: Single ventricle patients develop aortopulmonary collaterals (APC) whose flow (APCF) has been shown, in a cross-sectional study, to be inversely proportional to cerebral blood flow (CBF). Serial longitudinal CBF and APCF data in Fontan patients taking into account brain injury (BI) has never been reported. Decreased CBF may adversely impact neurodevelopmental outcome. Methods: A prospective longitudinal cohort of 27 Fontan patients (age 10 + 1.9 years, 74% male) underwent cardiac and brain MRIs 3-9 months after Fontan and 6.0 + 1.86 years afterwards to measure CBF, APCF and to assess BI (grouped into focal brain injury (FBI), generalized insult (GI) and hemorrhage). CBF was measured using jugular venous flow and APCF was measured by the difference between aortic flow and caval return. A multivariate linear regression model was used to assess the relationship between change in APCF and change in CBF controlling for time since Fontan, sex, and changes in BI. Results: Demographics, flow and BI data are shown in table 1. A strong inverse relationship was found between CBF and APCF when CBF was indexed to aortic flow and APCF was indexed to BSA (R^2 = 0.72, P<0.01). Overall, CBF decreased by 9 + 11% and APCF decreased by 0.73 + 0.67 l/min/m^2 (12% when indexed to aortic flow). CBF and APCF were significantly and inversely related when adjusting for time since Fontan, sex, and change in the visibility of BI on MRI. Each one unit increase in APCF was associated with an 8% decrease in CBF. Change in CBF was smaller for those with longer times since Fontan and was larger for males. Change in CBF was larger for those whose FBI or GI became less visible, but smaller for those whose hemorrhages became less visible. See table 2. Conclusion: CBF and APCF are inversely related across serial imaging, adjusting for time from Fontan, sex and BI. This may adversely impact neurodevelopment. As APCs can be embolized, this may be a modifiable risk factor. A large scale trial is warranted.