|Abstract||The current work examined the association between existential isolation and religious quest orientation (i.e., spiritual belief uncertainty) in four experiments. Specifically, Study 1 demonstrated a positive association between quest religiosity and trait existential isolation. In Study 2, there was no change in existential isolation scores as a function of priming quest uncertainty (vs. control conditions). However, supplemental results found that quest was associated with reduced existential isolation. An additional goal of this work was to explore the associative link between quest orientation, existential isolation, and well-being outcomes. Using path modeling, Study 3 found that, contrary to the first experiment, greater quest religiosity was associated with lower existential isolation, which in turn, predicted increased well-being. Study 4 attempted to build on the third experiment by promoting a sense of shared experience (i.e., I-sharing). Although the I-sharing condition did not influence isolation, the same general trend emerged in that heightened quest uncertainty contributed to better well-being through reduced isolation beliefs. Taken together, these results suggest a complex picture when examining existential isolation among the religiously skeptical, and that their openness and acceptance may lead to better ability to cope with isolation.