OBJECTIVE: To examine the relationship between total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) with disability and physical performance. METHOD: Wave 1 data were from Costa Rican Longevity and Healthy Aging Study ( n = 2,827). Lipoprotein profiles were measured using blood samples. Disability and physical functioning were measured with activities of daily living/instrumental activities of daily living (ADLs/IADLs) and objective assessment of physical performance. RESULTS: Lower HDL-C was associated with greater ADL disability, and lower TC with longer time to pick-a-pencil and Time-Up-Go (TUG) test. Age interacted between (a) TG and lung function, chair stands, and pick-a-pencil, and (b) HDL-C and TUG. Stratification showed lower TG and longer time picking up a pencil only for those above 84 years. Based on significant interactions with sex, lower TC was associated with slower chair stand time in women and higher HDL-C with slower chair stand time in men. DISCUSSION: Lower levels of lipoproteins may suggest worse physical function, but the association may differ by sex.