BACKGROUND: Ethylene oxide (EO) is a widely used industrial chemical recognized for its health risks, potentially posing threats to human health, including neurotoxicity, cardiovascular damage, and carcinogenic effects. Neurofilament light chain (NfL) is a protein released into the blood following axonal damage. To date, no studies have investigated the relationship between EO exposure and NfL levels. Therefore, we selected 5,902,013-2014 National Health and Nutrition Examination Survey (NHANES) participants to examine the relationship between blood EO levels and serum NfL concentrations. METHODS: According to the data from NHANES, this cross-sectional study used multiple regression analysis, subgroup analysis, and smooth curve fitting to explore the relationship between Ethylene oxide and Neurofilament light chain. RESULTS: The results of the present study indicate a positive association between EO exposure and NfL concentrations. Greater EO exposure was correlated with increased serum NfL concentrations in the fully adjusted model [ CONCLUSION: Our results indicate a link between increased EO levels and higher serum NfL concentrations in a sample of US adults aged 20 years and older. Although the directionality and clinical significance of this observation remain uncertain, our results emphasize the importance of conducting additional studies to investigate the possible causes and neurological effects of exposure to EO in adults.