This study proposed that, among older adults, higher support and lower strain received from each of the four relational sources (spouse/partner, children, family, and friends) were associated with reduced loneliness and improved well-being and that loneliness might mediate the relationship between support/strain and well-being. Structural equation modeling was conducted using a national sample of adults aged 50 years and older (N = 7,367) from the Health and Retirement Study. Findings indicated that support from spouse/partner and friends alleviated loneliness, while strain from all the four sources intensified loneliness; higher support and lower strain from various sources directly and indirectly improved well-being, with indirect effects mediated through reduced loneliness. It was concluded that, in later life, various sources of support/strain engender distinct effects on loneliness and well-being, and loneliness serves as one of the psychological pathways linking support/strain to well-being.