Direct support professionals (DSPs) are instrumental to the daily operations of organizations that support people with intellectual and developmental disabilities (IDD). With extensive responsibilities, DSPs often experience high levels of stress and burnout that can result in turnover and vacant positions. Self-care is the practice of behaviors that promote well-being, counter work-related stress, and foster resilience. The current study explored self-care and resilience, and their relationship with professional quality of life (i.e., satisfaction, burnout, and secondary traumatic stress) among DSPs. Using a convenient sample, 153 DSPs (71% female) completed an online survey comprised of multiple measures. Results indicated that DSPs often engaged in self-care behaviors across physical, psychological, emotional, spiritual, relational, and workplace domains, however, less than 40% engaged in self-care behaviors directly related to work. On average, DSPs reported high levels of resilience. Collectively, self-care and resilience accounted for 12% to 28% of variance in DSPs' professional quality of life. Given the contribution of self-care to resilience and professional quality of life, an active approach by IDD organizations to foster self-care among DSPs may help promote their longevity and retention.