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Soluble α-Klotho (s-Klotho) is a circulating protein with pleiotropic effects that mainly induce protective effects. Our study investigates the associations between s-Klotho and several established inflammatory biomarkers, with the aim of examining whether s-Klotho levels are representative of inflammatory states. A total of 11,128 eligible participants from NHANES 2007–2016 were included in our study. Levels of four inflammatory biomarkers, uric acid (UA), C-reactive protein (CRP), white blood cell (WBC) count, and mean platelet volume (MPV), were examined for their relationship with s-Klotho levels. Sub-analyses sorted the total population by gender and into four quartiles. Linear regression models were used to evaluate the strengths of associations. All four inflammatory biomarkers were significantly associated with s-Klotho levels. UA, CRP, and WBC count showed an inverse association, while MPV showed a direct one. Of the four markers, UA was most strongly correlated with s-Klotho levels (β coefficient: −28.89 in unadjusted model,  p &lt;.001), and this relationship was stronger in women than in men (β coefficient of UA in men: −22.01,  p &lt;.001; in women: −31.54,  p &lt;.001). In addition, all four biomarkers manifested stronger associations with s-Klotho in higher quartiles, and the highest absolute values of β coefficients appeared in Q4 vs. Q1. s-Klotho is significantly associated with well-recognized inflammatory biomarkers. A decrease in s-Klotho levels implies a general inflammatory status; therefore, s-Klotho serves as a potential biomarker that is inversely correlated with inflammatory conditions. Further applications in clinical practice will provide us with a better understanding of its role.Key messagesSoluble α-Klotho (s-Klotho) levels are significantly associated with the inflammatory markers uric acid, C-reactive protein, white blood cell count, and mean platelet volume.S-Klotho is involved in inflammatory processes and plays a protective role.S-Klotho may serve as an inverse indicator of inflammation. Soluble α-Klotho (s-Klotho) levels are significantly associated with the inflammatory markers uric acid, C-reactive protein, white blood cell count, and mean platelet volume. S-Klotho is involved in inflammatory processes and plays a protective role. S-Klotho may serve as an inverse indicator of inflammation.

Soluble klotho as an effective biomarker to characterize inflammatory states