Multiple Sclerosis (MS) patients suffer from negative mood disorders and fatigue due to numerous psychological and physical symptoms and difficulty accepting their reality, which negatively impacts their quality of life. This study aimed to evaluate the effectiveness of Dohsa-based psychomotor rehabilitation enhanced with compassion therapy on fatigue severity in MS patients in Isfahan. This quasi-experimental study employed a pretest-posttest-follow-up design with experimental and control groups. The statistical population included all MS patients in Isfahan who had records at the MS clinic and association. Using purposive sampling, 30 patients were selected and divided into experimental (15 participants) and control (15 participants) groups. Before beginning treatment, patients completed the Fatigue Severity Scale (FSS) questionnaire, with assessments repeated during the post-test and follow-up phases. The experimental group received 10 sessions of Dohsa-based treatment enhanced with compassion therapy, conducted three times per week, with a follow-up assessment 30 days after the post-test. Analysis of the multivariate covariance results showed that psychomotor rehabilitation using the Dohsa method enhanced with compassion therapy significantly reduced fatigue levels in MS patients (P<0.001).