RationaleLoneliness is a global concern associated with adverse effects on cardiovascular disease (CVD) that may differ by nationality, collectivism, and gender. ObjectiveThis study examined whether associations between loneliness and CVD indicators (e.g., metabolic dysregulation [MetD], inflammation, sleep dysfunction) would vary by nationality, collectivism, and gender. We predicted that loneliness would be associated with poorer CVD values in (1) Japan than the United States (U.S.), (2) in individuals higher rather than lower in collectivism, and (3) our exploratory hypotheses about gender were that loneliness would interact with gender to be associated with differential CVD indicators in the U.S. versus Japan. MethodsParticipants (aged 36 to 78) from the MIDUS Refresher Biomarker (n = 644) and the MIDJA 2 Biomarker studies (n = 293) completed questionnaires, bloodwork, and a physical exam. U.S. participants were from multiple cities, and Japanese participants were from Tokyo. Loneliness was measured via responses to the question, “How often in the past week did you feel lonely?” Logistic regression and path analyses using structural equation modeling determined individual differences in loneliness, whether loneliness predicted CVD indicators, and whether nationality, collectivism, and gender moderated these associations. ResultsLoneliness was prevalent in the U.S. (25.39%) and Japan (20.82%). Unexpectedly, Japanese adults reported less collectivism than U.S. adults. We found significant interactions of (1) nationality and gender on MetD and inflammation, (2) gender and loneliness on sleep dysfunction, and (3) nationality and loneliness on MetD. Loneliness was associated with greater MetD in the U.S. but not in Japan. ConclusionsCultural influences on loneliness contradicted expectations and suggested caution when equating nationality with cultural values. Our Japanese sample was from Tokyo, which may have lower collectivism than rural Japanese regions. We recommend future studies consider geographic location when examining associations between loneliness, collectivism, and CVD.