Background: Approximately half of children receiving palliative care are under age five; however, there are a few studies exploring palliative care interventions for this population. The purpose of this study was to evaluate the effects of Reiki on pain, stress, heart, and respiratory rates, oxygenation, and quality of life (QoL) in hospitalized young children receiving palliative care services. Methods: In this single-group pilot study, hospitalized children receiving palliative care who were aged 1–5 years received two Reiki sessions per week for 3 weeks. Physiologic measures were assessed pre/post each session, and parent report measures of pain and QOL were collected at baseline, 3 weeks, and 6 weeks. The parent rating of Reiki's perceived efficacy and their own symptoms were also measured. Results: Sixteen families consented. Children had a mean age of 26 months and included nine boys and seven girls. Results were not significant but there were medium-to-large clinical effect sizes for children's QoL, stress, oxygenation, heart, and respiratory rates. Parents’ physical and mental health scores decreased over time. Children exhibited signs of relaxation such as quiet sleep post-Reiki versus active awake pre-Reiki session. Conclusion: Reiki is a noninvasive relaxing therapy that is useful for hospitalized young children receiving palliative care. The children reacted positively in both action and outcome measures. Multisite studies with larger sample sizes are needed to be able to generate enough scientific evidence to fully recommend Reiki as an adjunct for pain management.