ObjectiveTo investigate the status of quality of life and influencing factors among newly diagnosed epilepsy patients with co-morbid anxiety and depression. MethodsA total of 180 newly diagnosed epilepsy patients from June 2022 to December 2022 in a district of Shanghai were selected as the study subjects. The Quality of Life in Epilepsy-31 (QOLIE-31), Hamilton Depression Rating Scale (HAMD-24), Hamilton Anxiety Rating Scale (HAMA), and Epilepsy Self-Management Scale (ESMS) were used to assess patients' quality of life, depression levels, anxiety levels, and self-management abilities, respectively. Patients were divided into the co-morbid depression group (HAMA≥14 and HAMD>17) and the control group (HAMA<14 and HAMD≤17), and their general characteristics and scale scores were compared. Spearman correlation, Pearson correlation, and multiple linear regression analysis were used to identify influencing factors of quality of life in epilepsy patients with co-morbid depression. ResultsCompared to the control group, the anxiety comorbid with depression group of older adults had a higher proportion, higher unemployment rate, lower personal and family annual income in the past year, higher frequency of epileptic seizures, and lower medication adherence (P<0.05). The correlational analysis revealed a negative correlation between the quality of life abilities of epilepsy patients with comorbid anxiety and depression and the severity of anxiety and depression. (r=−0.589, −0.620, P<0.05). The results of multiple linear regression analysis showed that the frequency of seizures in the past year (β=−1.379, P<0.05), severity of anxiety (β=−0.279, P<0.05), and severity of depression (β=−0.361, P<0.05) have an impact on the ability to quality of life in epilepsy patients with co-morbid anxiety and depression. These factors account for 44.1% of the total variability in quality of life (R2=0.4411, P<0.05). ConclusionThe frequency of seizures in the past year, as well as the severity of anxiety and depression, are important factors that influence the ability to quality of life in epilepsy patients with comorbid anxiety and depression. For these patients, it is crucial to take into account these factors and provide appropriate support and interventions.