Obesity is a risk factor for stroke and neurodegenerative disease. Excess body fat has been linked to impaired glucose metabolism, insulin resistance, and impulsivity and may be a precursor to decline in attention and executive cognitive function. Here, we investigated the effects of high BMI on regional cerebral blood flow (rCBF) using single photon emission computed tomography (SPECT) imaging in healthy subjects. A total of 16 adult men and 20 adult women were recruited from the community between January 2003 and July 2009 as part of a healthy brain study (HBS) conducted at the Amen Clinics, a private medical facility. Participants in the study were screened to exclude medical, neurological, and psychiatric conditions, including substance abuse. Subjects were categorized as normal or overweight according to BMI. Using a two sample t-test, we determined the effects of BMI on rCBF in normal vs. overweight subjects. Subjects were matched for age and gender. Statistical parametric mapping (SPM) revealed a higher BMI in healthy individuals that is associated with decreased rCBF in Broadmann areas 8, 9, 10, 11, 32, and 44, brain regions involved in attention, reasoning, and executive function (P < 0.05, corrected for multiple comparisons). We found that an elevated BMI is associated with decreased rCBF in the prefrontal cortex of a healthy cohort. These results indicate that elevated BMI may be a risk factor for decreased prefrontal cortex function and potentially impaired executive function.