Other studies have previously demonstrated that perceived stress and maladaptive stress management can lead to harmful outcomes including depression, morbidity, and mortality. College students (especially freshmen) have more difficulty dealing with stress, which can increase their susceptibility to engage in high risk behaviors. The importance of conducting this research is to discover the effects that perceived stress levels may have on depression outcomes in college students, and to evaluate the influence of health related behaviors on this relationship. This study used a retrospective cross-sectional correlational design to examine correlations between perceived stress, physical activity, and other health behaviors on clinical and perceived depression in college students. A random sample of 20,000 students was drawn from 62,476 students enrolled at Arizona State University (ASU). Participants included 2,238 students who volunteered to take the American College Health Association-National College Health Assessment (ACHA-NCHA) in spring 2009. Supplemental questions for ASU students were developed by ASU Wellness and administered as a part of the ACHA-NCHA II. The university sent an invitation email, wherein students were directed through a hyperlink to the survey website. ACHA provided institutional survey data in an SPSS file for analysis. The data were evaluated with Spearman Rho Correlation Analysis and Wilcoxon-Mann-Whitney test. There were more female participants (n = 580) than males (n = 483), both averaged 23 years of age. Men had greater height, weight, and body mass index than females, all were significant mean differences. There were more significant correlations between health factors and having perceived depression than with having real or diagnosed depression. Logistic regression showed that out of all variables and behaviors studied, only high levels of stress, poor general health, substance use, and gender (female) resulted in significant odds in predicting that a participant would be in one of the depression categories. This research suggests that addressing these factors may be important to prevent and reduce depression among college students. This study provides empirical evidence that there is a significant relationship between perceived stress and depression among college students, and that health behaviors such as substance abuse have a negative mediating effect on this relationship.