Situations of vulnerability are associated with reduced life satisfaction. Although social support moderates the influence of situations of vulnerability, little is known about their associations. This study aimed to document situations of vulnerability and examine their association with life satisfaction among older adults, and the moderating effect of social support. Secondary analyses of cross-sectional data (n = 21,491; 73.4 ± 0.04) from the Canadian Longitudinal Study on Aging, stratified by sex. Confirmatory factor analysis identified a vulnerability variable from physiological, psychological, socioeconomic and social indicators. Regression models examined the associations. For both sexes, depressive symptoms, chronic conditions and insufficient income best explained vulnerability, followed by dependence in basic activities of daily living, less social participation and living with fewer people. Vulnerability was associated with lower life satisfaction, and social support acted as a buffer against vulnerability. The buffering effect of social support reinforces recommendations concerning policies and interventions designed to increase networks.