Although recent research suggests that the proportion of the US population identifying as non-religious has been rapidly expanding over the course of the last decade, relatively little research has examined the implications of this development for health and well-being. This study uses data from a large representative survey study of religion and health in the adult US population (N = 3010) to examine group differences among religious group members (N = 2401) and three categories of non-religious individuals: atheists (N = 83), agnostics (N = 189), and those stating no religious preference (N = 329). MANCOVA was used to analyze group differences on five outcome dimensions, incorporating 27 outcome variables. Religious non-affiliates did not differ overall from affiliates in terms of physical health outcomes (although atheists and agnostics did have better health on some individual measures including BMI, number of chronic conditions, and physical limitations), but had worse positive psychological functioning characteristics, social support relationships, and health behaviors. On dimensions related to psychological well-being, atheists and agnostics tended to have worse outcomes than either those with religious affiliation or those with no religious preference. If current trends in the religious composition of the population continue, these results have implications for its future healthcare needs.