To explore the changes of serum levels of thyroid hormones and their clinical significance in patients with perimenopause depression. Methods: Thirty-two patients with perimenopause depression (depression group), 30 perimenopausal patients with comorbidity of anxiety and depression (comorbidity group), 50 perimenopausal patients with anxiety disorders (anxiety group), and 85 perimenopausal normal controls (control group) were screened. The Hamilton Depression scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to assess the clinical symptoms of each subject. According to the presence or absence of negative perceptions, suicidal behaviors, and a ≥2 score on the third (suicide) item of the HAMD, the depression group and comorbidity group were further divided into the negative and non-negative subgroups. The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in fasting blood samples were measured and compared in all subjects. Results: The serum thyroid hormones levels in all groups were within the normal biological reference intervals. The serum levels of FT3 in the depression group and comorbidity group were significantly lower than those in the anxiety group (P<0.05) and control group (P<0.01); there was no significant difference in the serum levels of FT3 between the other groups (P>0.05). No significant difference in the serum levels of FT4 and TSH were found among the four groups (P>0.05). Compared to the non-negative subgroup, the negative subgroup in the depression group and comorbidity group showed a greater HAMD total score (P<0.01); there was no significant difference in the HAMA total score between the subgroups (P>0.05). There was no significant difference in serum FT3, FT4, and TSH levels between the negative and non-negative subgroups of the depression group and comorbidity group (P>0.05). In the negative subgroup of the depression group and comorbidity group, the serum FT3 level displayed a negative correlation with the HAMD total score (P<0.05). Conclusion: The serum levels of FT3 are decreased in perimenopausal women with depression, and in those with a risk of suicidal ideation and behavior, the decrease in FT3 level may be related to the severity of depression.