Social connection is important for people’s health and well-being. Social isolation arising from a lack of meaningful connection with others can result in deterioration of well-being with negative consequences for health. For people living with multiple long-term conditions, the building and maintaining of social connection may be challenging. The aim of this study was to explore with people with long-term conditions how they perceive they maintain and develop social connections. We undertook semi-structured interviews with seventeen adults, and analyzed the data for themes. Themes were “Meaningful connection”, “Wherewithal for social connection” and “Impact of a major change in life course”. The findings suggest that social connection is valued, and facilitates meaningful ways to reciprocate support with others, thus enabling access to knowledge and resources for better health and well-being. However, people with long-term conditions can experience challenges to developing and maintaining social connectedness after a major change in life course. We suggest that healthcare providers are well placed to facilitate ways for people with long-term conditions to socially connect with others in their neighbourhood and community, and that this in particular be attended to after a major life change.