Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers due to their excellent properties. The interference of OPEs on immune function has been proven, but the epidemiological data on OPEs exposure to related immune function diseases, such as sjögren syndrome (SjS), is limited. In cross-sectional study, 283 serum samples were collected from healthy individuals (n = 145) and patients with SjS (n = 138) in Hangzhou, China. Eight OPEs, triethyl phosphate (TEP), tributyl phosphate (TBP), tris (2-chloroethyl) phosphine (TCEP), triphenyl phosphate (TPHP), tri (1-chloro-2-propyl) phosphate (TCIPP), 2-ethylhexyldi-phenyl phosphate (EHDPP), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), and tri (2-butoxyethyl) phosphate (TBOEP), were frequently measured in serum samples. In addition, we explored the associations between the serum OPEs concentration and the risk of SjS. Results showed that TEP (mean controls 2.17 and cases 3.63 ng/mL) was the most abundant OPEs in the serum samples of the control and case groups, followed by TCIPP (mean controls 0.54 and cases 0.78 ng/mL). Serum TEP, TPHP, and EHDPP concentrations were positively correlated with SjS [odds ratio (OR): 1.97, 1.96, and 2.42, respectively; 95% confidence interval (CI):1.34–2.89, 1.34–2.87, and 1.34–2.87, respectively] in the adjusted model, and a negative correlation of TBP concentrations with SjS in the adjusted model (OR: 0.35, 95% CI: 0.17–0.70) was observed. Compared with the lowest quartile concentrations, the ORs of SjS at the highest quartile concentrations of TEP (OR: 4.93, 95% CI: 2.24–10.82) and TPHP (OR: 4.75, 95% CI:1.89–11.94) were significantly higher. This study suggests that human exposure to OPEs may increase the risk of SjS.