Background: The simultaneous effect of physical activity (PA) and smoking on pulmonary function in young people remains unclear. Propose: The aim of this study was to determine the influence of smoking and PA on pulmonary function in young university students in Cáceres, Spain. Methods: A sample of 120 young nursing students was studied (60 smokers and 60 nonsmokers). All subjects underwent spirometry with a COPD-6 portable device, and their level of PA was quantified using the International Physical Activity Questionnaire. The influence of PA and smoking on pulmonary function was determined by comparing hypotheses. Results: Significant differences were observed between smokers and nonsmokers in terms of percent forced expiratory volume in 1 second, percent forced expiratory volume in 6 seconds, lung age, and the difference between lung age and chronological age (LA–CA) in those who practiced mild PA. In the subjects who performed moderate and vigorous PA, these differences were not noted. In the intragroup analysis, significant differences were observed in smokers in terms of percent forced expiratory volume in 1 second, percent forced expiratory volume in 6 seconds, lung age, and LA–CA; however, in the control group, differences were only observed in terms of lung age and LA–CA. These findings were confirmed in the multivariate analysis. Conclusions/Implications for Practice: Our findings confirmed a deterioration in pulmonary function in smokerswho did not perform moderate or vigorous PA. The level of PA performed was positively related to pulmonary function in smokers, whereas in nonsmokers, improvements were only significant in LA–CA.