In this study, we proposed that people understand major life events in terms of spiritual as well as psychological, social, and physical dimensions. Specifically, we examined the possibility that life events that are perceived to be sacred losses or violations of the sacred (i.e., desecrations) have significant implications for the health and well-being of the individual. A total of 117 adults, randomly selected from a community, identified the most negative life event they had experienced in the past two years. They then completed measures of the degree to which they appraised this event as a sacred loss and as a desecration, as well as measures of religious coping, the impact of the event, and four sets of criteria: traumatic impact, physical health, emotional distress, and growth. These hypotheses were largely supported. Sacred loss and desecration were unrelated to physical health. However, they were tied to higher levels, though somewhat differential patterns, of emotional distress. While sacred loss was predictive of intrusive thoughts and depression, desecration was tied to more intrusive thoughts and greater anger. Furthermore, sacred loss was linked to greater posttraumatic growth and positive spiritual change; in contrast, desecration was associated with less posttraumatic growth. The links between the spiritual appraisals and outcomes were partially mediated by positive and negative methods of religious coping. These findings underscore the importance and multidimensionality of the spiritual meanings people attribute to major life stressors.