This study explores the relationship between religiosity, spirituality, and loneliness in the United States, using the 2018 General Social Survey to assess their interactions against a backdrop of declining traditional religious affiliation and a rise in “spiritual but not religious” identification. It examines religion and spirituality’s capacity to counteract loneliness, a condition with significant health implications. The analysis uncovers complex relationships between aspects of religious life and loneliness, showing no mitigating role of spirituality when controlling for other factors, with complex and varied negative relationships of religious service attendance and self-rate religiosity to different aspects of loneliness. Yet, any potentially protective effect of religion varies, with minority religious groups reporting feelings of increased loneliness. These findings underscore religion and spirituality’s nuanced roles in emotional well-being, indicating that their benefits (or not) against loneliness are complex, varied, and depend on the aspect of religion or loneliness observed, along with non-religious factors. The paper contributes to the literature on societal loneliness, changing religious and spiritual engagements, and highlighting the need for a comprehensive approach to explore the role of religion and spirituality in understanding loneliness specifically, and personal and social well-being more generally.