The incidence of papillary thyroid carcinoma (PTC) is constantly increasing in the global population, with no systematic screening. The current challenge is to define relevant risk factors contributing to this increase and to facilitate an early diagnosis. Selenium (Se) is an essential trace element required for proper thyroid function. Selenium deficiency has been associated with papillary thyroid carcinoma, but a comparison of different biomarkers of Se status is missing. Plasma samples of patients and controls were analyzed for three markers of Se status: total plasma Se by total reflection X-ray fluorescence, selenoprotein P (SELENOP) by ELISA, and activity of glutathione peroxidase 3 (GPX3) by enzyme assays. Total plasma Se and GPX3 were significantly lower in patients than in controls (78.1 ± 16.7 µg/L vs. 94.7 ± 19.5 µg/L, P < 0.0001, and 200.6 ± 42.7 U/L vs. 239.2 ± 36.7 U/L, P < 0.0001, respectively). All plasma biomarkers showed significant positive correlations, supporting sample integrity, analytical quality and insufficient Se status. A predictive model was deduced, indicating a significant association between low plasma Se and PTC (OR=5.02, 95%; CI:1.51-16.73; P = 0.009). The results support the hypothesis that Se status is affected by thyroid cancer, that thyroid cancer risk increases in case of Se deficiency, or that the interrelationship is interconnected. As Se deficiency is an addressable health risk, longitudinal studies are required to elucidate the direction of interaction and for testing protective measures.