Medical students experience more stress than the general population, which over time can cause mental and physical disease, including burnout. Identib,ing factors impacting stress during early medical training could inform strategies to minimize its impacts throughout training and in clinical practice. This study surveyed 238 first-year osteopathic medical students to assess stress (Perceived Stress Scale; PSS), grit, sleep quality (Pittsburgh Sleep Quality Index; PSQI), physical activity (Godin-Shephard LeisureTime Physical Activity Score; LTPA), and nutrition habits (Rapid Eating Assessment for Participants; REAP) within the first 2 weeks of starting medical school and again 10 weeks later. Incomplete responses were removed, leaving 204 study participants. We observed statistically significant decreases in grittiness (Delta grit = -2.230%, P = .002) and physical activity (Delta LTPA = -22.147%, P < .0001), while perceived stress (Delta PSS = 34.548%, P < .0001) and poor sleep quality (Delta PSQI% = 19.853, P < .0001) increased. Correlation analyses identified the strongest relationships were between Delta PSS vs Delta PSQI (r = .47, P < .0001) and Delta PSS vs Delta LTPA (r = - .20, P < .01). Multivariable linear regression analysis isolated Delta PSQI (P < .0001) and Delta LTPA (P = .012) as statistically significant predictors of Delta PSS. These results suggest early, repeated curricular interventions focused on physical activity and sleep hygiene may help students better manage stress during medical education.