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Objective: Poor sleep is associated with higher levels of inflammatory biomarkers. Conventionally, higher average time awake, lower average time asleep, and lower sleep efficiency define poor sleep. Recent research suggests that, in addition to average sleep, sleep inconsistency is an important indicator of sleep dysfunction. The current study sought to extend our knowledge of the relationship between sleep and inflammation through an examination of sleep inconsistency and inflammatory biomarkers.Methods: Secondary analyses of the Survey of Midlife in the United States (MIDUS) sleep study were conducted. Five hundred thirty-three individuals completed nightly sleep diaries, actigraphy, and underwent a blood draw for the inflammatory biomarkers C-reactive protein, interleukin-6, and fibrinogen. Sleep inconsistency was derived from 7 consecutive nights of assessment and was operationalized as nightly fluctuations in the following variables: terminal wakefulness, number of awakenings, time in bed, sleep onset latency, and wake after sleep onset. Structural equation modeling was used to examine the influence of a latent average sleep and a latent sleep inconsistency variable on a latent inflammation variable. Models were subsequently adjusted for age, sex, BMI, health, and medication. Stratified models by sex were also analyzed.Results: The average sleep model would not converge. The sleep inconsistency model fit the data well. A significant positive association between the latent factors sleep inconsistency and inflammation was observed (β = 10.18, SE = 4.40, p = 0.021), suggesting inconsistent sleep is associated with higher levels of inflammatory biomarkers. When stratified by sex, the association between the latent sleep inconsistency factor and inflammation was significant for women (β = 1.93, SE = 0.82, p = 0.018), but not men (β = 0.20, SE = 0.35, p = 0.566). The association between sleep inconsistency and inflammation weakened following multivariate adjustment (β = 6.23, SE = 3.71, p = 0.093).Conclusions: Inconsistent sleep may be an associated feature of inflammatory dysfunction, especially in women. Future studies should build upon this preliminary work and examine these associations longitudinally and through treatment trials.