© 2017 The Obesity Society Objective: To assess associations between nonalcoholic fatty liver disease (NAFLD) and measures of brain health in a population-based sample of adults. Methods: Participants from the CARDIA study (Y25 exam; age 43-55 years) with concurrent computed tomography quantification of liver fat, visceral adipose tissue (VAT), and brain magnetic resonance (MR) images were included (n = 505). NAFLD was identified after exclusion of other causes of liver fat. Total tissue volume (TTV) and gray matter cerebral blood flow (GM-CBF) were estimated using 3T brain MR images. Results: NAFLD prevalence was 18%. NAFLD was associated with lower TTV and GM-CBF after adjusting for intracranial volume, demographics, and health behaviors (P < 0.04 for all). In models with additional adjustment for cardiovascular risk factors, the association of NAFLD with GM-CBF remained significant (P = 0.04) but was attenuated after adjustment for VAT (P = 0.06) and eliminated with BMI (P = 0.20). NAFLD was not associated with TTV after adjustment for cardiovascular risk factors (P = 0.10) or additional adjustment for VAT (P = 0.14) or BMI (P = 0.05). Conclusions: NAFLD is negatively associated with early brain health as assessed by MR measures of structure (TTV) and perfusion (GM-CBF). BMI and VAT attenuated this relationship, providing insight into the potential metabolic role of liver fat in brain health and disease.