© 2016, © The Author(s) 2016. Adolescence is considered a critical period for risk of depressive symptoms, with prevalence ranging from 13% to 34%. Few studies have examined the relationships among perceived stress, bullying, and depressive symptoms accompanied by a biological marker of stress (cortisol). The purpose of this pilot study was to determine the feasibility of collecting biological specimens in a high school setting, including a morning and afternoon sample of salivary cortisol as well as computer-based survey data in order to examine the relationships among these variables in ninth-grade adolescents. A convenience sample of 31 ninth-grade students from a Southern suburban high school participated in this cross-sectional, correlational study. Perceived stress contributed the most toward the variance in depressive symptoms (F = 29.379, df = 1, p <.001, partial eta square [ η2p ] = 0.583). Females (n = 15) had higher depressive symptoms scores than males, n = 16; t(29) = −2.94, df = 29, p =.023. Bullying scores were low and not significantly correlated with depressive symptoms, but participants reported more verbal/relational bullying as compared to physical, cultural, or cyberbullying. Cortisol slopes were normal (a negative change) for 20 participants (64.5%), while 4 (12.9%) had a blunted cortisol slope (less than.01 μg/dl change from morning to afternoon) and 7 (22.36%) had an opposite cortisol slope (morning low and afternoon high). Data collection procedures (salivary cortisol and computer-based surveys) were feasible in a school setting. High rates of perceived stress and depressive symptoms warrant a larger study in the future.