The purpose of this study was to examine the relations between fatigue, family function and self-esteem among middle-aged women in menopausal periods. Data were collected through self-administered questionnaire survey form 133 middle-aged women. The data collection was done from March 2nd to April 10th, 2012. As a results, there were significant differences in fatigue by education level and menstrual status. And, there were significant differences in family function according to education level and marital status. Also, there were significant differences in self-esteem by education level, marital status and monthly income. Fatigue was negatively related to family function and self-esteem. And family function was positively related to self-esteem. These results suggest that nursing intervention should be developed to strengthen family function and self-esteem as a way to regulate fatigue for middle-aged women in menopausal periods. Especially, it is necessary to pay more attention to health management of middle-aged women belonging to menopausal transition, with low-income, low-education level.