Background: Excessive Daytime Sleepiness (EDS) is positively associated with the risk of cardiovascular disease (CVD) events and CVD mortality. However, the association between EDS and subclinical markers of CVD, such as arterial stiffness, is not fully understood and could have implications for CVD screening. EDS is multifactorial in origin, thus we incorporated measures of exhaustion and fatigue in order to comprehensively assess the association of lethargy and central artery stiffness. We examined the separate relationships between EDS, exhaustion, fatigue, and aortic stiffness via carotid-femoral pulse wave velocity (cfPWV) in a large population-based study. Methods: A cross-sectional analysis of ARIC Study participants (n=2500, mean age: 79.7, 57.2% female) who underwent arterial stiffness measurements (cfPWV) and completed the Epworth Sleep Scale (ESS) questionnaire in 2016-2019. EDS was defined as ESS 11. Exhaustion was derived from the Center for Epidemiological Study’s Depression (CES-D) scale, with positive exhaustion corresponding to increased effort in daily activities and noticeable difficulty in getting “going’. Fatigue was assessed at annual follow up calls in 2012-2013 and calculated as a summary score with participants responses about feeling tired in various scenarios in the past 7 days noted as a numeric value (1-5: never, rarely, sometimes, often or always). We used multivariable linear regression to estimate the association between ESS, exhaustion, and fatigue with cfPWV, adjusting for age, race-study center, body mass index, diabetes, heart rate, mean arterial pressure, and blood-pressure medication use. We evaluated potential effect modification by race, sex, diabetes, and hypertension. Results are presented as unstandardized beta coefficients (β) and 95% confidence intervals (CI). Results: A total of 14.2% participants reported EDS, 17.2% reported exhaustion, and the average fatigue score was 8.0. ESS was not associated with cfPWV when adjusting for covariates (β; 95% CI: -1.4; -4.7, 1.9). Similarly, EDS was not associated with cfPWV (β; 95% CI: -4.9; -40.4, 30.6), nor was there an association between ESS quartiles and cfPWV. However, both exhaustion (β; 95% CI: 40.4; 7.8, 73.0) and fatigue (β; 95% CI: 5.4; 0.6, 10.3) were positively associated with cfPWV after adjusting for covariates. There was no evidence of effect modification by race, sex, diabetes, or hypertension. Conclusion: EDS was not associated with arterial stiffness. A (positive) association was observed for both exhaustion and fatigue with cfPWV, suggesting a need for further investigation of fatigue related conditions and arterial stiffness in older adults.