Importance: Spiritual well-being is an important aspect of health-related quality of life for persons with chronic illnesses such as multiple sclerosis (MS), yet research on interventions remains limited.

Objective: To assess the feasibility of an occupational therapy intervention addressing the spiritual well-being of people with MS.

Design: Mixed-methods program evaluation using theoretical thematic analysis of qualitative data.

Setting: Community center serving people with MS in a midwestern U.S. city.

Participants: A total of 42 participants attended at least one session; 22 participants provided qualitative data. Ten met the inclusion criteria for quantitative analysis, including completion of pretest and posttest measures and attendance of at least half of the sessions.

Intervention: Making Meaning, a group intervention based on the Model of Occupational Wholeness, was conducted over eight weekly 45-min sessions. The focus was on exploring and integrating spiritual practices into daily life.

Outcomes and Measures: Participants completed the Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being 12-Item Scale (FACIT–Sp–12) to measure spiritual well-being and answered open-ended questions. Attendance was recorded and the facilitator and observers provided qualitative observations.

Results: Pretest–posttest comparisons of FACIT–Sp–12 scores indicated a moderate improvement in spiritual well-being (d = 0.41). Attendance and qualitative data supported the intervention’s feasibility and suggested areas for refinement.

Conclusions and Relevance: Making Meaning is a feasible intervention, showing promise for promoting spiritual well-being for people with MS. Further research is warranted.

Plain-Language Summary: This study introduces a practical and acceptable occupational therapy group intervention, Making Meaning, which shows promising potential for improving the spiritual well-being of people with multiple sclerosis.

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