Following preventive behaviors is a key measure to protect people from infectious diseases. Protection motivation theory (PMT) suggests that perceived risk motivates individuals to take protective measures. The COVID-19 pandemic has posed unprecedented stress to the public, and changes in perceived risk may be more pronounced among college students than among other groups due to the related campus lockdown. With 1,119 college students recruited as research subjects, a quantitative research was conducted in Wuhan, China, to deduce the relationship between the perceived risk and preventive behavior of college students, as well as between the mediation effect of individual affect and the moderating effect of physical exercise. The results showed that the preventive behavior of college students was significantly affected by perceived risk, and both positive affect and negative affect played a mediating role between perceived risk and preventive behavior. Specifically, positive affect aided the relationship between perceived risk and preventive behavior, negative affect was detrimental to their relationship, and the mediation effect of positive affect is significantly higher than that of negative affect. Furthermore, physical exercise played a moderating role in the mediation effects of positive affect and negative affect. Therefore, appropriate measures should be taken to strengthen Chinese college students' perceived risk and provide them with corresponding guidance. The importance of physical exercise should also be emphasized to help college students with low perceived risk reduce negative affect, increase positive affect, and promote their preventive behavior.