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Mothers are primary caregivers and gatekeepers for family health yet little is known about the nature and level of maternal concern, social support, and health-related quality of life for mothers across the maternal continuum. This research was designed to examine the relationship between maternal concerns and health-related quality of life, describe the impact of social support on this relationship, identify the relationship between sociodemographic factors and concern, social support and HRQOL, and identify differences in these variables among categories of mothers. Participants were 238 mothers from Maryland, West Virginia, and Pennsylvania who completed a mail survey. The sample was composed primarily of married women with at least some college or technical training who were the biological mothers of one or two children, working full-time, and living in families with incomes at or above {dollar}45,000. All participants completed the Everyday Stressors Index, the Medical Outcomes Study Social Support Survey, and the Medical Outcomes Study Short Form 36 version 2® (SF-36v2). Mothers of children of all ages reported a low level of concern and moderate level of social support; level of maternal concern demonstrated a small to moderate negative relationship with HRQOL and was the strongest predictor of HRQOL compared to sociodemographic factors and social support. Social support did not moderate the relationship between maternal concerns and HRQOL and demonstrated a minimal mediating influence on the relationship between concern and the mental health subscale of the SF36v2®. Income and education were the sole sociodemographic predictors of HRQOL. There were no significant differences in concern, social support or HRQOL among four groups of mothers categorized by age of oldest child living at home. Participant scores on the mental health subscales of the SF-36v2 differed significantly from gender and age-matched national norms. Results indicate the need to focus attention on the mental health needs of mothers of children of all ages. Recommendations for nursing practice include periodic screening for changes in mental health and education, anticipatory guidance, and advocacy efforts to assist mothers to cope with commonly identified concerns. Recommendations for nursing research include longitudinal studies that pair self-report data with neurohormonal markers.