The primary objectives were to investigate the association of physical activity levels with 1) loneliness and social isolation; 2) protective factors: resilience, purpose-in-life, and perception of aging; and 3) the impact of these factors on healthcare expenditure patterns across physical activity levels. The study sample was identified from adults age >65 who completed a health survey in 2018 or 2019 (N=6,652). Among survey respondents, the prevalence of low, moderate, and high physical activity levels was 29%, 31%, and 41%, respectively. Moderate and high physical activity were associated with 15%-30% lower likelihoods of loneli-ness and social isolation; and with 27% to 150% higher protective factors. In addition, physical activity was associated with the mitigation of increased healthcare expenditures associated with loneliness, social isola-tion, and low levels of protective factors. Thus, physical activity could serve as an intervention to reduce lone-liness and social isolation, augment protective factors, and mitigate excess healthcare expenditures.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)