Very little has been empirically explored on the association between spirituality and work stress in the academic setting; thus, this study involving full-time education faculty of colleges in Cagayan de Oro City was conducted. Standardized tools were used to determine the levels of spirituality and work stress. An in-depth interview with the top and lowest ten on spirituality was conducted to further validate the findings. This study’s findings reveal that the faculty’s extent of work stress was low. As to spirituality, they considered themselves highly spiritual. Moreover, the study showed that age, gender, educational attainment, and length of teaching experience did not significantly influence the teachers’ level of work stress. However, only gender was found to have a significant influence on the faculty’s level of spirituality. Finally, no statistical evidence was found that the faculty’s level of spirituality had a significant effect on their level of work stress. However, results of the in-depth interview reveal the practical significance of spirituality in relation to work stress. Therefore, the findings offer insight into the limitation of empirical study to measure objectively the spiritual domain of man. Hence, the role of spirituality still cannot be dismissed despite the lack of statistical evidence.