This study examined the moderating role of self-compassion in the relationship between stress and psychological well-being among Catholic priests in Enugu Diocese, Nigeria. A total of 200 priests participated, completing standardized measures of perceived stress (PSS-10), psychological well-being (RPWB-18), and self-compassion (SCS-SF). Using a cross-sectional correlational design and Hayes’ PROCESS macro, the results showed that stress negatively affected several dimensions of psychological well-being, especially environmental mastery and self-acceptance. Self-compassion was positively related to autonomy, personal growth, purpose in life, and self-acceptance. Importantly, self-compassion significantly moderated the relationship between stress and psychological well-being in the domains of autonomy, environmental mastery, and self-acceptance, reducing the negative effects of stress. These findings highlight the importance of incorporating self-compassion practices into pastoral care and seminary training to improve emotional resilience and psychological health among clergy.