Vaping and e-cigarettes are popular with young adults due in part to the perception of harm reduction compared to traditional cigarette smoking. Vaping offers a safer alternative to cigarette smoking but still can promote pathological changes that diminish the health and lifestyle activities of frequent users. Aerobic exercise improves cardiovascular health, but the influence of physical activity upon vaping-associated pulmonary injury (VAPI) is poorly understood. The long-term goal of this study is to assess the impact of aerobic exercise upon VAPI. Cohorts of male (n=4) and female (n=4) C57BL/6 in four treatment groups consisted of: 1) no exercise, no vape; 2) no exercise, vape; 3) exercise, no vape; and 4) exercise and vape. Physical activity on voluntary running wheels was measured four days per week by tracking the number of wheel revolutions per evening. Vape aerosol exposure was performed using an automated inhalation apparatus (SCIREQ InExpose) equipped with JUUL pens loaded with commercially purchased Peach Ice flavored juice (ORGNX; zero nicotine) for 4 hours per day and 5 days per week. Results demonstrate that exercise performance is reduced by vape aerosol exposure after 4 weeks compared to the running-only cohort. Both sexes initially show increased exercise performance with acclimation to the running wheels within the first few weeks with female mice consistently running approximately 2 miles more than corresponding males 7.33 versus 9.25 miles for females versus males, respectively. Variability between individual mice was evident, but vaping led to a substantial decrease in distance run for both females and males after 4 weeks 13% and 12.5% lower, respectively. These findings demonstrate that vaping impairs aerobic exercise capacity with sex-specific differences in outcomes. Ongoing studies will determine the mechanistic basis for aerobic exercise's impact upon VAPI using a combination of molecular, histologic, and functional analysis. In conclusion, females appear initially more resistant to VAPI than males, but this advantage may be lost with prolonged exposure.