Patterns of decreased resting cerebral blood flow (CBF) within the inferior temporal gyri, angular gyri, and posterior cingulate are a feature of aging and Alzheimer’s disease (AD) and have shown to be predictive of cognitive decline among older adults. Fitness and physical activity are both associated with many indices of brain health and may positively influence CBF, however, the majority of research to date has examined these measures in isolation, leaving the potential independent associations unknown. The purpose of this study was to determine the unique contributions of fitness and physical activity when predicting CBF in cognitively healthy adults at risk for AD. One hundred participants (63% female) from the Wisconsin Registry for Alzheimer’s Prevention underwent a maximal exercise test, physical activity monitoring, and a 3-D arterial spin labeling magnetic resonance imaging scan. For the entire sample, fitness was significantly associated with CBF while accounting for physical activity, age, gender, APOE ε4, family history of AD, education, and handedness (p = .026). Further, fitness explained significantly more variance than the combined effect of the covariates on CBF (R2 change = .059; p = .047). These results appear to be gender dependent, our data suggest fitness level, independent of physical activity, is associated with greater CBF in regions that are known to decline with age and AD for female (p = .011), but not male participants.