Compassion fatigue is a serious concern among individuals in the helping professions, including animal welfare. Current interventions for compassion fatigue are time-consuming, expensive, and not well understood. Similarly, the role of personal resources in popular models of occupational stress and health are not well understood. The present study investigated three novel positive psychology mechanisms (self-compassion, psychological flexibility, and work-related psychological flexibility) independently as moderators in the job demands-resources framework of occupational stress and health. Subsequently, a pilot randomized controlled field trial explored whether an intervention aimed at increasing self-compassion led to decreased compassion fatigue, increased job engagement, and more psychologically flexible among staff in animal sheltering. While cross-sectional findings failed to support significant moderator effects, psychological flexibility and work-related psychological flexibility emerged as incremental predictors of emotional exhaustion and engagement, respectively. Though high levels of attrition from the treatment group limited power to detect significant time by treatment effects for the pilot RCT, intent-to-treat analyses suggested significant sample-level gains in self-compassion and psychological flexibility. Analyses also revealed that psychological flexibility increased via increases in self-compassion. Future directions for JD-R research as well as a thorough discussion of methodological considerations surrounding future development of the pilot intervention are provided.