Recent studies have reported a strong association between blood pressure (BP) and resting energy expenditure (REE). However, it is not known whether this relationship persists over time. Therefore, the authors examined the temporal relationship between REE and systolic BP. In addition, the impact of sympathetic tone and anthropometric variables on this relationship was examined. All testing was performed on healthy, overweight African American and European American women aged 25 to 45 years over 4.5 years in the University of Alabama at Birmingham General Clinical Research Center. Repeated-measures mixed-models revealed REE as a significant determinant of systolic BP (β=0.0155, P<.0001), independent of catecholamines, leg fat, visceral fat, fat-free mass, fat mass, height, relative skeletal muscle index, and resting heart rate. Observations that REE is predictive of systolic BP across 4.5 years support previous findings that REE may potentially mediate resting BP, independent of anthropometric variables and a marker for sympathetic tone. © 2014 Wiley Periodicals, Inc.