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Objectives. — This study aimed to investigate skill-based sexual enhancement counseling on quality of life (QOL) of women with multiple sclerosis.Methods. — The present study was a quasi-experimental research. Forty-four patients with multiple sclerosis and their spouses (n = 88) voluntarily participated in this study based on the inclusion and exclusion criteria. The subjects in the intervention group (n = 22 couples) received the skill-based sexual enhancement counseling program in six sessions. Both groups completed three stages of pretest-posttest, and the standard MSQOL54 questionnaire 3 months later. Data were analyzed by SPSS-20 using descriptive and inferential statistics (repeated measures ANOVA, chi-squared test, and t-test).Results. — Psychological quality of life (P = 0.001) and overall QOL (P = 0.008) were significant after 3 months. According to the findings, the skill-based sexual enhancement counseling program was effective on the quality of life enhancement.Conclusions. — According to the findings, skill-based sexual enhancement counseling program iseffective in quality of life enhancement. Therefore, it is recommended to health care providersto use enhancement program alongside the other rehabilitation and medical services to improvethe Multiple Sclerosis patients’ quality of life.