Introduction The role of serum cholesterol in the pathogenesis of Parkinson's disease (PD) remains unclear. The objective of this study was to assess the association between serum cholesterol and PD in a cohort of statin-free newly diagnosed PD patients. Methods This retrospective study used fasting lipid profiles obtained from 672 consecutive statin-free newly diagnosed PD individuals and 540 controls. These PD individuals were identified from three medical institutions during 2017-2021, and the controls were identified from three physical examination centers during the same time period. Logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment of age, sex, and tobacco use history. Results Among 672 PD individuals, 112 were excluded in accordance with the current criteria, leaving 560 PD patients. The multivariate binary logistic regression analysis showed that LDL-C was the only variable contributing to the occurrence of PD (OR 1.39, 95% CI: 1.07-2.31, p < .001) after adjusting for age, sex, and tobacco use history; this association persisted following further adjustment for TC and HDL-C. In the subgroup analysis of the adjusted results of LDL-C after correcting for TC and HDL-C, lower LDL-C was associated with a higher risk of PD. Conclusion Among selected populations of statin-free newly diagnosed PD individuals, low LDL-C might be associated with the occurrence of PD.