Background: Stress among pharmacy students could greatly affect their learning activities and general well-being. It is therefore necessary to investigate how stress relates with the quality of life of students to maintain and/or improve their personal satisfaction and academic performance. A school-based longitudinal study was used to investigate the relationship between stress and quality of life of undergraduate pharmacy students. The 10-item perceived stress scale and the shorter version of the WHO quality of life scale were administered to the same participants at two time points i.e. Time 1 (4 weeks into the semester) and Time 2 (8 weeks afterwards). The correlations and differences between the study variables were tested using the Pearson's coefficient and independent sample t test. Results:The mean stress scores were higher at Time 2 compared to Time 1 for the first and second years. However, there was no significant difference in stress for different year groups-Time 1 [F (3) = 0.410; p = 0.746] and Time 2 [F(3) = 0.909; p = 0.439]. Female students had higher stress scores at Time 2 compared to male students. The main stressors identified in the study were; large volume of material to be studied (88.2%), laboratory report writing (78.2%), constant pressure to maintain good grades (66.4%) and the lack of leisure time (46.4%). Even though most students employed positive stress management strategies such as time management (68.2%), other students resorted to emotional eating (9.1%) and alcohol/substance use (1.8%). At Time 2, perceived stress scores were significantly negatively correlated with social relationship (r = −0.40, p ≤ 0.0001), environmental health (r = −0.37, p ≤ 0.0001), physical health (r = −0.49, p ≤ 0.0001) and psychological health (r = −0.51, p ≤ 0.0001). Conclusion:The study reported significant correlations between stress and various domains of quality of life of undergraduate pharmacy students. It is thus necessary to institute some personal and institutional strategies to ameliorate the effect of stress on the quality of life of pharmacy students while encouraging the use of positive stress management strategies.