OBJECTIVE: This study aimed to investigate the incidence of overweight in patients with major depressive disorder (MDD) comorbid anxiety during the acute phase and to explore associated factors. DESIGN: Cross-sectional study. SETTING: Wuhan Mental Health Center, China, from July 2017 to August 2022. PARTICIPANTS: 737 hospitalised patients diagnosed with MDD in the acute phase with comorbid anxiety symptoms. PRIMARY OUTCOME MEASURES: Incidence and clinical correlations of overweight (body mass index (BMI) ≥ 24). RESULTS: Among the study population, 55.63% were classified as overweight. Binary logistic regression analysis revealed that being married (B=0.28, p value=0.018, OR=1.10), thyroid-stimulating hormone (TSH) levels (B=0.10, p value=0.001, OR=1.10) and low-density lipoprotein cholesterol (LDL-C) levels (B=1.61, p value=0.045, OR=1.18) were significant positive predictors of overweight. Additionally, multiple linear regression indicated that TSH levels (B=0.16, t=3.17, p value=0.002) were positively associated with higher BMI values. CONCLUSION: Over half of the hospitalised MDD patients with comorbid anxiety are overweight. Thyroid function emerges as a crucial clinical factor for overweight in this population. Targeted interventions focusing on thyroid function may be a promising approach for managing overweight in these patients.