Faith leaders who are working to promote justice and healing in Colombia might confront stressful circumstances that challenge their spiritual meaning systems and limit ministry-related quality of life. However, whether focusing on domestic or international samples, research has not examined potential effects of spiritual struggles on ministry-related quality of life. In total, 166 faith leaders who were serving in Christian churches and organizations in Colombia completed a Spanish version of Exline, Pargament, Grubbs, and Yali’s (2014) Religious and Spiritual Struggles Scale along with assessments of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) symptomatology. The relative frequencies of different types of spiritual struggles in the sample were as follows: divine = 5.4%, morality = 29.9%, ultimate meaning = 18%, interpersonal = 18%, and doubting = 16.2%. Bivariate results revealed that severity of each of these struggles was concurrently linked with more mental health symptomatology as well as less compassion satisfaction and greater secondary traumatic stress in relation to ministry-related experiences. In addition, when accounting for symptom severity of PTSD and MDD, structural equation modeling results revealed that participants who were experiencing greater moral struggles were particularly vulnerable for struggling in their ministry role at the time of this study. These findings support the need for more research on this topic as well as the possible development of strategies for addressing the emotional, spiritual, and educational needs of faith leaders in Colombia and other nations who are serving persons in contexts of trauma, loss, and displacement.