Purpose <p>To investigate the relationship between serologically abnormal lipid metabolism parameters and the onset of dysthyroid optic neuropathy (DON) in patients with thyroid-associated ophthalmopathy (TAO).</p> Methods <p>A total of 183 patients clinically diagnosed with TAO in the Department of Endocrinology of our hospital from February 2019 to September 2023 were retrospectively enrolled, comprising 34 in the DON group and 149 in the non-DON group. We collected serological lipid metabolism parameters, thyroid function, fasting blood glucose, and other clinical parameters and compared these between the two groups. Multivariable logistic regression analysis was exploited to identify the risk factors associated with the occurrence of DON in patients with TAO.</p> Results <p>Patients in the DON group exhibited higher age (<i>P</i> &lt; 0.001) and a greater proportion of men (<i>P</i> = 0.028) than those in the non-DON group. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose levels were elevated in patients with DON (<i>P</i> = 0.004, <i>P</i> = 0.068, and <i>P</i> = 0.026, respectively). Additionally, the proportions of high serum TC (35.3% vs. 15.4%, <i>P</i> = 0.008) and high serum LDL-C (26.5% vs. 11.4%, <i>P</i> = 0.023) were significantly higher in the DON group than in the non-DON group. Multivariable logistic regression analysis indicated that age and serum TC were independently associated with the onset of DON in patients with TAO (odds ratios = 1.069 and 2.120, respectively; both <i>P</i> &lt; 0.05).</p> Conclusion <p>Hypercholesterolemia might be associated with the development of DON, suggesting that high serum TC be strictly managed to reduce the risk of DON in patients with TAO.</p>