Background: According to decreased self-esteem in multiple sclerosis (MS) patients, it is necessary to utilize appropriate methods in order to improve self-esteem in MS patients. So this study was conducted on patients with MS supported by the Iranian MS society in 2001 for determining the effect of self-care program on their self-esteem. Materials & Methods: In this semi-experimental study 34 patients with MS who were not in the acute phase of disease were selected. The data were collected via personal questionnaires, problem list, Cooper and Smith standard questionnaire for self-esteem and self report checklists. The validity of Cooper and Smith questionnaires was approved in Iran and the validity of demographic questionnaires was then approved using a pilot study on first 10 samples revealing a high correlation coefficient (r=0.93). Self-care program was performed for one month period and the data were analyzed using paired t-test, Wilcoxon, Croscal-Wallis and Manwithney tests. Results: Application of self-care program improved the self-esteem and reduced some symptoms such as muscular spasm, fatigue, constipation, loss of memory and amnesia in MS patients. The mean valve of self-esteem increased from 54 before performing the program to 68 after the program (P<0.05). Conclusion: Using self-care program can be an effective method for improving self-esteem of MS patients.