Background: Major Depressive Disorder (MDD) exhibits significant gender disparities in prevalence. Previous studies have indicated that differential patterns of sympathetic nervous system activation in different gender may contribute to varying cardiovascular/cerebrovascular risks in MDD, though underlying factors remain unclear. In this study, we aim to investigate the association between subjective sleep alterations, blood pressure, emotional state, and gender specific sympathetic activation in MDD. Methods: We collected and analyzed ECG data from 50 female and 25 male age-matched, first-episode, drug-naive MDD patients. Autonomic nerve function was assessed using Heart Rate Variability (HRV). Subjective sleep indicators of SE, SOL, short sleep, and poor sleep quality were evaluated utilizing the Pittsburgh Sleep Quality Index (PSQI). Emotional characteristics were quantified via the Hamilton Depression Scale-17 (HAMD-17) and Hamilton Anxiety Scale (HAMA). Resting systolic (SBP) and Diastolic Blood Pressure (DBP) were also measured upon arrival. Results: In male MDD patients, each 1% reduction in SE was associated with a 0.350ms decrease in SDNN. In females, each 1-minute reduction in SOL was associated with a 0.004-unit increase in LF/HF ratio; while short sleep (< 6h) was associated with increased RMSSD and pNN50 (all p ? 0.048). Reduced DBP in males correlated with different patterns (decreased pNN50 and HF (nu); increased LF (nu) and LF/HF ratio) (all p ? 0.033). In females, only reduced SBP was associated with each 1-mmHg decrease linked to a 0.040-unit increase in LF/HF ratio. Conclusion: Subjective sleep disturbances exhibit disparity in gender-specific patterns of sympathetic-vagal balance in MDD. However, blood pressure reduction consistently correlated with sympathetic activation across both genders, revealing distinct autonomic-mediated pathophysiological pathways that may underlie differential cardiovascular susceptibility in MDD.