BackgroundTwo related lifestyle behaviors associated with sleep disturbance are sedentary behavior and physical exercise participation. We aimed to use a population-based study to disentangle the relationships between sedentary behavior, exercise, and sleep disturbance based on blood-cell-based inflammatory biomarkers.MethodsA total of 22,599 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the analyses. Sleep disturbance was assessed according to the NHANES questionnaire. Exercise participation ansd sedentary behavior were evaluated by the global physical activity questionnaire. The inflammatory biomarkers in the examination were white blood cell (WBC) count, neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). A complex multistage sampling design and weighted multivariable logistic regression were applied for further analysis. Mediation models were constructed to figure out the mediating role of inflammatory biomarkers.ResultsThe weighted prevalence of sleep disturbance was 24.17%. Sedentary behavior and exercise were associated with sleep disturbance after full adjustment [for sedentary behavior, OR (95% CI): 1.261 (1.154, 1.377); for exercise, OR (95% CI): 0.849 (0.757, 0.953)]. In severe sedentary behavior groups, the mitigation effect of exercise on sleep disturbance was observed [OR (95% CI): 0.687 (0.551, 0.857)]. For the mechanism, strong associations were detected between inflammatory biomarkers and sleep disturbance. Mediation analysis showed that WBC, NEU, NLR, and SII mediated the statistical association between sedentary behavior and sleep disturbance with proportions (%) of 2.09, 2.27, 1.76, and 0.82, respectively.ConclusionsOur data suggested that sedentary behavior was a risk factor for sleep disturbance. Blood-cell-based inflammatory biomarkers were an easily accessible and cost-effective strategy for identifying sleep disturbance and also significantly mediated the association between sedentary behavior and sleep disturbance. Exercise was proved to be effective in severe sedentary behavior groups to improve sleep disturbance symptoms, while the internal mechanism needed further exploration.