Background: This study examined the distribution of stress-cortisol responses and risk factors affecting perceived stress and cortisol responses among 187 university students in South Korea. Methods: Perceived stress, depressive symptoms, and health-promoting lifestyle were assessed using structured questionnaires. Blood analyses and anthropometrics were used to determine cortisol and cardiometabolic risks. Multinomial logistic regression analysis was used to examine the factors affecting stress-cortisol responses. Results: Four groups of stress-cortisol responses were found, including normal (39.0%), high stress (34.8%), high stress-cortisol (13.9%), and high cortisol group (12.3%). Age, systolic blood pressure, high-density lipoprotein cholesterol, depressive symptoms, and physical activity were associated with stress-cortisol responses. Conclusions Multidimensional interventions are needed to reduce stress levels and promote normal stress-cortisol responses.