Admission to a professional program marks the beginning of fulfilling a career goal. However, the rigors of professional education can be demanding. Stress, depression, and anxiety (SDA) can interfere with learning, affect academic performance, and impair clinical practice performance. Studies report a general increase in the severity of and extent of mental health problems among college/university students. The literature regarding nursing students' mental health distress identifies academic and personal sources of stress and coping efforts, with emphasis on the stress and anxiety associated with clinical practice. This cross-sectional descriptive exploratory study investigated levels of SDA among nursing students in 3 years of a university-based program. The association between quality of life indicators including known stressors, such as financial concerns and balance between school and personal life, and SDA was also investigated. Through an online survey, 437 participants from one mid-western Canadian undergraduate nursing program completed the Depression Anxiety Stress Scales and provided data on quality of life indicators and demographic information. Participants also were invited to provide narrative data about their experiences with SDA. This article will present significant findings including: levels of SDA; comparisons between our sample and a normative sample on the dimensions of SDA; and the results of multiple regression analysis identifying significant predictors of each dimension. Themes from the qualitative comments from 251 of the participants were identified and added depth and clarity to the quantitative findings. The predominant themes represented were: perceptions of clinical practice, coping, personal issues, and balancing school, work, and personal life. Implications and recommendations for curriculum design, ensuring students understand program expectations prior to admission, and enhancing accessibility to mental health/support services need to be considered.