Introduction: Undergraduate and graduate medical education both have been reported to have high rates of depression, anxiety, and burnout as a result of the rigors of their educational curricula. Wellness, including physical fitness, is important to the profession because it may help mitigate these increased rates of depression and anxiety. While several studies examine physical fitness and academic performance in primary and secondary education, few studies have examined the association between fitness and performance in health professions education. Given the demands of medical school, this investigation aimed to investigate the possibility of an association between physical fitness and body mass index (BMI) with academic performance. Another goal was to examine the change in physical fitness and BMI throughout medical school. Materials and Methods: Standardized measures of physical fitness were examined in 192 Army students from the Uniformed Services University of Health Sciences over 4 years from the classes of 2017–2019. Measurements include (1) body composition (BMI); (2) muscular endurance (timed push-ups); (3) aerobic endurance (timed run), and (4) total fitness defined as total points from sit-ups, run, and push-ups (everything but BMI). Pearson correlation analysis was conducted between physical fitness and academic performance measures such as United States Medical Licensing Examination (USMLE) Step 1, USMLE Step 2 Clinical Knowledge (CK), and average core clerkship National Board of Medical Examiners (NBME) exam scores. A repeated measures analysis of variance was conducted to examine the differences of students’ fitness total points and BMI over 4 fitness measurements spanning approximately 1.7 years. Results: There were weak positive correlations, 0.20 and 0.22, between USMLE Step 2 CK exam scores and push-up points and total fitness points, respectively. There also were weak positive correlations, 0.21 and 0.24, between core clerkship average NBME exam scores and push-up points and total fitness points, respectively. No statistically significant change of individual students’ fitness total point change was observed (F(2.52, 334.93 = 1.37, P = 0.26)). There was also no individual BMI change (F(2.36, 274.21 = 2.78, P = .06)) over the first four assessment measurements (about 1.7 years lapse). However, the class means over the four measurements showed a decrease of fitness total points and an increase of BMI. Conclusions: Our investigation suggests that there may be correlations between physical fitness and clinical exam performance such as USMLE Step 2 CK and average core clerkship NBME exams. Although there is no statistically significant change in individual fitness total points or BMI, the study suggests that physical fitness and BMI may decline during medical school. This may be as a result of increasing academic demands while balancing clinical duties from clerkship rotations.