Study Objective: Inflammation may represent a common physiological pathway linking both short and long sleep duration to mortality. We evaluated inflammatory markers as mediators of the relationship between sleep duration and mortality in community-dwelling older adults. Design: Prospective cohort with longitudinal follow-up for mortality outcomes. Setting: Pittsburgh, Pennsylvania, and Memphis, Tennessee. Participants: Participants in the Health, Aging and Body Composition (Health ABC) Study (mean age 73.6 ± 2.9 years at baseline) were sampled and recruited from Medicare listings. Measurements and Results: Baseline measures of subjective sleep duration, markers of inflammation (serum interleukin-6, tumor necrosis factor-α, and C-reactive protein) and health status were evaluated as predictors of all-cause mortality (average follow-up = 8.2 ± 2.3 years). Sleep duration was related to mortality, and age-, sex-, and race-adjusted hazard ratios (HR) were highest for those with the shortest (< 6 h HR: 1.30, CI: 1.05-1.61) and longest (> 8 h HR: 1.49, CI: 1.15-1.93) sleep durations. Adjustment for inflammatory markers and health status attenuated the HR for short (< 6 h) sleepers (HR = 1.06, 95% CI = 0.83-1.34). Age-, sex-, and race-adjusted HRs for the > 8-h sleeper group were less strongly attenuated by adjustment for inflammatory markers than by other health factors associated with poor sleep with adjusted HR = 1.23, 95% CI = 0.93-1.63. Inflammatory markers remained significantly associated with mortality. Conclusions: Inflammatory markers, lifestyle, and health status explained mortality risk associated with short sleep, while the mortality risk associated with long sleep was explained predominantly by lifestyle and health status.