Intense emotional demands of oncology nursing create a stressful work environment and increase the likelihood of leaving. The study aims to explore, describe, and understand how pediatric hematology/oncology nurses caring for chronically ill or dying patients use their spirituality to cope with job stress, maintain spiritual well-being (SWB), and continue to work in this specialty. A concurrent mixed-method research design consisted of a web-based survey and interview. Data collection included demographics, intent to leave questions, and four valid and reliable research instruments measuring spirituality, stress, coping, and SWB. A responsive interview guide directed interviews. Quantitative analysis ( = 130) revealed moderate to high levels of spirituality, moderate stress, coping, and SWB. Stress and SWB were weakly, inversely correlated ( = -.221,  = .011) indicating lower stress was associated with greater SWB. Coping and SWB were weakly, positively correlated ( = .248,  = .005) indicating greater coping was associated with greater SWB. An intent to leave in the next year was reported by 5.4%. Emerging themes from qualitative data ( = 22) included faith-informed or existential spirituality, work environment, and emotional/psychological stressors such as feeling overwhelmed or witnessing suffering and coping through self-care and spirituality. Dimensions of SWB included spiritually based coping and life’s meaning and purpose. Intent to leave was related to the work environment or travel distance. A nurse’s spirituality offers a mechanism for coping with accumulated losses and grief encountered in clinical practice and in turn supports SWB.

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