BACKGROUND: The health implications of trace elements have become increasingly concerning, yet the connection between blood manganese levels and anemia remains insufficiently examined. This research endeavors to explore the potential linkage between blood manganese concentrations and anemia. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, this study examines the correlation between blood manganese levels and anemia among U.S. adults, offering a comprehensive national perspective. The study included 11,300 adults aged 20 and above, with both blood manganese and hemoglobin levels measured. Generalized Additive Model (GAM) was applied to delineate smooth curves, and threshold effect analysis was performed to identify the inflection points of these curves. Subsequently, unconditional logistic regression was employed to assess the risk. RESULTS: Our research involved a total of 11,300 individuals, among which 1,143 (10.1%) were identified with anemia. The curve fitting analysis indicated a U-shaped relationship between blood manganese levels and the risk of anemia. Specifically, when blood manganese levels were below 8.69 µg/L, increasing concentrations were linked to a decreased risk of anemia, with an adjusted OR of 0.838 (95% CI: 0.735-0.954), indicating a protective effect of this level of blood manganese against anemia. Conversely, when blood manganese levels were at or above 8.69 µg/L, further elevations were strongly associated with an increased risk of anemia, with the adjusted OR rising to 1.160 (95% CI: 1.124-1.196), suggesting that excessively high blood manganese levels significantly raised the risk of developing anemia. CONCLUSION: This study provides novel insights into the association between blood manganese levels and anemia. Further extensive, population-based cohort studies are necessary to validate the causality and to uncover the intrinsic toxicological mechanisms.