Objective To investigate the effect of ozone autohemotherapy on serum lipoprotein（a） ［Lp（a）］，sleep quality，and heart rate variability in postmenopausal patients with hypercholesterolemia. Methods This study is a prospective cohort study. A total of 100 postmenopausal female patients diagnosed with hypercholesterolemia during health check-ups at the South Lake Campus of Wuhan Wuchang Hospital between August 2024 and May 2025 were selected. They were randomly divided into a control group and a treatment group，with 50 patients in each group. Two patients dropped out of the control group，and four patients dropped out of the treatment group. The control group received atorvastatin calcium tablets，while the treatment group received ozone autohemotherapy in addition to the treatment in the control group. The treatment lasted for 10 days per cycle，and both groups were treated and observed for one month. The levels of Lp（a），total cholesterol （CHO），high-density lipoprotein cholesterol （HDL-C），low-density lipoprotein cholesterol （LDL-C），triglycerides （TG），uric acid （UA），homocysteine （Hcy），and fasting plasma glucose （FPG），as well as Pittsburgh Sleep Quality Index （PSQI） scores and heart rate variability were compared before and after treatment between the two groups. Correlation analysis was conducted to evaluate the relationship between Lp（a），PSQI scores，and heart rate variability after treatment in both groups，along with the incidence of adverse reactions. Results After treatment，the serum Lp（a），CHO，and LDL-C levels in the treatment group were significantly lower than before treatment （P < 0.01 or 0.05），but no statistically significant difference was found between the two groups （P > 0.05）. The PSQI scores in both groups were significantly reduced compared to before treatment，with the treatment group showing a more significant decrease than the control group （P < 0.05）. In the treatment group，standard deviation of the averages of 5-minute RR interval （SDANN）， standard deviation of RR interval （SDNN）， and the root mean square of the difference between adjacent RR interval （rMSSD） were significantly higher compared to both before treatment and the control group at the same time，with statistical significance （P < 0.01 or 0.05）. After treatment， there was no correlation between Lp（a） levels and SDANN， SDNN， or rMSSD. PSQI scores were negatively correlated with SDANN， SDNN， and rMSSD （P < 0.01）. Conclusions Ozone autohemotherapy has a regulatory effect on lipid metabolism and autonomic nervous function in postmenopausal women. The improvement in autonomic nervous function may be associated with the enhancement of sleep quality.