Background <p>Patients with anxious depression (AD) are often associated with abnormal lipid levels, and no studies have been conducted on the prevalence of abnormal lipid levels in first-episode and drug-naïve (FEDN) AD patients and whether there are gender differences. The aim of this study was to conduct a large-scale clinical cross-sectional study to investigate the prevalence of abnormal lipid levels in patients with AD, the presence of gender differences, and related influencing factors.</p> Methods <p>This study included 1380 Han Chinese patients aged 18–60&#xa0;years with first-episode and drug-naïve anxious depression (FEDN AD). A self-created questionnaire was utilized to obtain demographic and clinical data. The patients’ clinical symptoms were assessed using the Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), and the Positive and Negative Symptom Scale (PANSS) positive subscale. In addition, we measured the patients' BMI, thyroid hormone, blood glucose, blood pressure and lipids levels.</p> Results <p>The prevalence of abnormal lipid levels was higher in FEDN AD patients (83.3%), and there was no gender difference (male 83.6% vs. female 83.2%). In addition, binary logistic regression analysis showed that HAMD score and TSH levels were significant predictors of abnormal lipid levels in male and female AD patients.</p> Conclusions <p>The prevalence of abnormal lipid levels is higher in FEDN AD patients, and there is no gender difference. Higher TSH and depression levels were strongly associated with abnormal lipid levels in both male and female AD patients. This indicates the importance of strengthening health education, regular diet, appropriate exercise, regular review of relevant indicators, attention to abnormal lipid levels and alertness to adverse consequences in this population.</p> <p><i>Trial registration</i> This work includes data from a registration clinical trial (ID: 2016-Y27).</p>