Abstract There is a paucity of data regarding the use of non‐pharmacologic therapies for pain in sickle cell disease. The purpose of this pilot study was to assess the acceptability and feasibility of video‐guided mindfulness meditation, breathing exercises, and yoga, in addition to standard of care, during admission for painful vaso‐occlusive crisis. Feasibility was demonstrated by the enrollment rate of > 90% and high level of participant engagement in the intervention. Acceptability was demonstrated by positive feedback obtained in post‐intervention surveys and the majority of subjects who expressed interest in participating in future mindfulness and yoga therapy sessions.