Objective: To explore the effect of citalopram combined with mirtazapine on sleep regulation and relief of depressive symptoms in patients with sleep disorders caused by depression. Methods: 100 cases of patients with sleep disorders caused by depression who were admitted to our hospital from June 2023 to June 2025 were selected, they were according to the digital random table method divided into two groups , 50 cases in the control group were treated alone with citalopram, 50 cases in the observation group were treated with citalopram and mirtazapine，the sleep regulation effects, relief effects of depressive symptoms, overall therapeutic effects and adverse reactions of the two groups were compared. Results: In the observation group, the total score of the pittsburgh sleep quality index (PSQI) after treatment was (9.89±1.21) points, which was lower than (12.68±1.08) points that of the control group (P<0.05). In the observation group, the scores of the 17-item hamilton depression scale (HAMD-17) after treatment were (11.38±1.20) points，the clinical overall impression scale-severity of Illness (CGI-S) was (3.32±0.42) points，which were lower than (13.49±1.12) points and (4.11±0.45) points in the control group (P<0.05). In the observation group, the total effective rate (94.00%) was higher than control group (80.00%) (P<0.05). There was no statistically significant difference in adverse reactions between the observation group (6.00%) and the control group (4.00%) (P>0.05). Conclusion: When treating sleep disorders caused by depression, the combined use of escitalopram oxalate and mirtazapine can further enhance the effect of sleep regulation and relief of depressive symptoms, achieving a good overall therapeutic effect and having ideal safety.