Objective: The purpose of this study was to investigate the effectiveness of stress management training with Iranian-Islamic spiritual therapy on stress, anxiety, and depression in women with fibromyalgia. Method: the Research method was semiexperimental with two-group and three-stage (pre-test-post testfollow up). Among the statistical population of women with fibromyalgia, 30 patients were selected in Isfahan according to the criteria for entering the research and were randomly assigned to the experimental group (n = 15 = under the educational program; Stress management with Iranian-Islamic spiritual therapy content was assigned to 12 sessions once a week), and control group (n = 15 = no intervention). All participants completed the Depression, Anxiety and Stress Measurement Scale (21DASS) in three stages of the baseline, after implementation of Iranian-Islamic spiritual therapy and at the follow-up stage. Result: The results of repeated measure analysis of variances showed that stress-management program with Iranian-Islamic spiritual therapy content after intervention and follow-up (45 days after baseline measurement) had a significant effect on reduction of stress, anxiety, and depression (p<0. 01). Conclusion: According to the results of this study, stress management training with Iranian-Islamic spiritual therapy content is an effective method for reducing the severity of stress, anxiety, and depression in women with fibromyalgia.