Multiple sclerosis (MS) is a chronic neurological disease that not only affects the patient but also has a considerable impact on marital relationships and the quality of life of spouses. This study investigated marital quality in the spouses of men with MS. This descriptive comparative study included 82 men registered with the MS Association of Shiraz, Iran, and their spouses; and 82 healthy men and their spouses. The participants were selected using the convenience sampling method. Data on marital quality were collected using the Perceived Relationship Quality Components inventory. The validity and reliability of this inventory has been previously confirmed in Iran. Data analysis was performed using SPSS software, version 21. The significance level was set at p < 0.05. The mean (± standard deviation) age of the men with MS was 35.9 ± 9.69 years and the mean duration of the relationship with their spouse was 14.24 ± 3.85 years. The total score for the Perceived Relationship Quality Components inventory and scores for the components satisfaction, passion, intimacy, and love were significantly lower in the spouses of men with MS compared with the spouses of healthy men (p < 0.001). For spouses of men with MS, the disease negatively impacts the marital relationship quality, particularly in terms of satisfaction, passion, intimacy, and love. Therefore, to improve the quality of life and marital relationships in MS patients and their spouses, it is important to include couple-based educational programs and marital therapy in rehabilitation programs for MS.