Background <p>The current study was to investigate the associations of missing teeth or lost functional tooth units (FTUs) with circadian syndrome and the mediated effects of systemic inflammation as indicated by serum C-reactive protein (CRP).</p> Methods <p>Dentition examination, high-sensitivity serum CRP, and circadian syndrome data of 11,490 participants aged 18–80 years from US National Health and Nutrition Examination Survey 2015–2020 were analyzed. Generalized linear model and mediation effect model were used.</p> Results <p>After adjusting confounders, the numbers of missing teeth or lost FTUs and Ln-transformed CRP were positively associated with higher circadian syndrome prevalence (odds ratio and 95% confidence interval: missing teeth: 1.01(1.00, 1.01), <i>P =</i> 0.043; lost FTUs: 1.02(1.01, 1.03), <i>P =</i> 0.001; CRP: 1.23(1.20, 1.26), <i>P</i> &lt; 0.001). Furthermore, positive associations between the numbers of missing teeth or lost FTUs and Ln-transformed CRP but inverse association between implant prosthesis and Ln-transformed CRP were observed after adjustment (β ± standard error: missing teeth: 0.012 ± 0.002; lost FTUs: 0.024 ± 0.005; implant prosthesis: -0.136 ± 0.053). Moreover, significant mediation effects of serum CRP were observed in the associations of missing teeth or lost FTUs with circadian syndrome. The mediated proportions (%) for missing teeth or lost FTUs were 32% and 20% respectively.</p> Conclusions <p>Missing teeth or lost FTUs were positively associated with serum CRP and circadian syndrome in US adults. Systemic inflammation partly mediated the association of missing teeth or lost FTUs with circadian syndrome.</p> Clinical relevance <p>Maintaining more natural teeth may be associated with lower circadian syndrome prevalence.</p>