Background: The purpose of this study was to determine if a relationship exists between physical activity or Body Mass Index (BMI) and academic performance in college-age students. Both physical activity and BMI have shown to impact academic performance in younger students, but data for college-age students is limited. Methods: Between October and December 2006, data were collected from 98 biochemistry students at the University of Nebraska-Lincoln. Analysis was performed on 77 students who had complete outcome data. Physical activity measures were categorized to reflect those who met and those who did not meet the Centers for Disease Control and Prevention (CDC) and American College of Sports Medicine (ACSM) recommendations for physical activity [1]. BMI was calculated from each student’s height and weight recordings. Academic performance was determined by each student’s cumulative college Grade Point Average (GPA) and score on the ACT examination. The means were compared using test for two groups and general linear models. Where statistically significant results existed, groups were compared using the Tukey multi-test procedure. A one-sample comparison of means was conducted for fitness between our sample and the age-matched American population as stated by the Healthy People 2010 Report [1]. Results: Students in the normal BMI category had significantly higher GPA and ACT scores than students in the overweight category. Juniors had significantly higher GPA and ACT scores than seniors. Our findings did not differ between our sample and the American population with regards to recommendations for fitness by the CDC and ACSM. Conclusions This study demonstrated that normal weight individuals, had higher GPA and ACT scores than their overweight counterparts, underscoring the need to intensify interventions focused on reducing and preventing obesity among school-age populace.