Abstract Background: Social isolation in cancer survivors associates with diminished quality of life and worse survival. However, effects of loneliness on medical expenditure are understudied. We examined associations of loneliness with medical costs, and social/psychological/behavioral determinants of health (SDHs). Methods: We identified 1,866 cancer survivors from the 2021 Medical Expenditure Panel Survey. One has loneliness if answering ‘often’ for any of: feel lack companionship/left out/isolated from others. Two-part regression models assessed marginal effect of loneliness to annual total health care expenditure (cost) in cancer survivors, aged 18-64 (young) and ≥65 years (older), adjusting for age, sex, race, region, education, health insurance, comorbid illnesses, family income, unemployment, and activity limitation. Models were sequentially adjusted for every single SDH. Ordinal regression models assessed associations of loneliness with SDHs. Results: Over one-tenth of young (19%) and older (13%) cancer survivors reported loneliness. Loneliness was associated with higher cost in older cancer survivors (conditional coefficient (CC) 0.46, 0.12-0.81), but not young survivors (-0.14, -0.62-0.36). In both age groups, cancer survivors with loneliness more often reported stress, lack of help, as well as less time talking on the phone and getting together with support persons (Table). In older patients, sequential adjustment for stress, expected help, get-togethers, or church attendance decreased effect of loneliness to cost; among which get-togethers showed the greatest decrease (CC 0.28, -0.03-0.62). Conclusions: Loneliness was associated with higher total medical expenditure in older US cancer survivors. Findings warrant further study of personal or community support to mitigate loneliness, in an effort to reduce healthcare costs and financial burden in older cancer survivors. Age (year) 18-64 (648) ≥65 (1223) Loneliness No (505, 81%) Yes (143, 19%) No (1046, 87%) Yes (177, 13%) Mean Age (years) 56 56 75 74 Female % 64.5 66.4 53.0 59.1 Non-white % 23.1 21.8 15.8 26.4 Federal poverty level < 100%, % 7.4 18.9 8.9 7.2 Comorbidities ≥ 3, % 25.4 44.4 60.4 67.1 Unemployment ≥ 1, % 35.8 45.3 83.3 89.6 < high school % 30.8 33.7 37.7 36.6 Conditional coefficient (95% CI) Ref -0.14 (-0.62-0.36) Ref 0.46 (0.12-0.81) Odds ratio (95% CI) of loneliness to SDHs Stress Ref 8.42 (5.20-13.63) Ref 6.82 (4.72-9.87) Lack of help - family 3.46 (2.32-5.14) 2.61 (1.88-3.60) Lack of help - friends 3.25 (2.00-5.29) 1.92 (1.36-2.72) Lack of help - community 2.45 (1.64-3.66) 2.16 (1.58-2.96) Times of talk on phone 0.55 (0.36-0.85) 0.77 (0.55-1.07) Times of get together 0.34 (0.21-0.55) 0.38 (0.25-0.58) Citation Format: Fangyuan Chen, Ryan Nipp, Xuesong Han, Zhiyuan Zheng, Robin Yabroff, Changchuan Jiang. Effects of loneliness on medical expenditures among US cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2250.