Midlife is filled with challenges and unique stressors for women, which necessitate a greater understanding of the factors that influence their life satisfaction. This study examined the relationship of family strains/changes and weight to life satisfaction, as mediated by family coping, physical activity, sleep and health stress. The findings indicated that women in midlife, who experienced more stressful life changes and had higher body mass index scores, slept fewer hours and had greater health stress, which resulted in lower life satisfaction. These results have implications for family health professionals and programmes that deal with family and health problems, including sleep, weight and stress. Copyright © 2011 John Wiley & Sons, Ltd.