Objective. To assess the health-related quality of life (HRQoL) of student pharmacists and explore factors related to HRQoL outcomes of student pharmacists in a doctor of pharmacy (PharmD) program at a public university. Methods. A survey instrument was administered to all student pharmacists in a PharmD program at a public university to evaluate differences and factors related to the HRQoL outcomes of first-year (P1), second-year (P2), third-year (P3), and fourth-year (P4) student pharmacists in the college. The survey instrument included attitudes and academic-related self-perception, a 12-item short form health survey, and personal information components.Results. There were 304 students (68.6%) who completed the survey instrument. The average health state classification measure and mental health component scale (MCS-12) scores were significantly higher for P4 students when compared with the P1through P3 students. There was no difference observed in the physical component scale (PCS-12) scores among each of the 4 class years. Significant negative impact on HRQoL outcomes was observed in students with higher levels of confusion about how they should study (scale lack of regulation) and concern about not being negatively perceived by others (self-defeating ego orientation), while school satisfaction increased HRQoL outcomes (SF-6D, p<0.001; MCS-12, p=0.013). A greater desire to be judged capable (self-enhancing ego-orientation) and career satisfaction were positively associated with the PCS-12 scores (p<0.05). Conclusion. Factors associated with the HRQoL of student pharmacists were confusion regarding how to study, ego orientation, satisfaction with the chosen college of pharmacy, and career satisfaction. First-year through third-year student pharmacists had lower HRQoL as compared with P4 students and the US general population. Support programs may be helpful for students to maintain or improve their mental and overall health.