Background: Depression is the commonest psychiatric disorder in women. Menopausal symptoms include hot flashes, sleep disturbance, irritability, and vaginal dryness, which can give rise to depression in postmenopausal women. Objectives: This study aimed to determine the factors affecting and associated with depression in postmenopausal women. Patients and Methods: In this descriptive analytical research, 250 postmenopausal women who referred to health centers in Ahvaz were selected through an easy sampling method and studied. The beck depression inventory, the menopause rating scale (MRS) Questionnaire, and demographic information sheets were used to collect data. The collected data were analyzed with Pearson correlation coefficients, Spearman, chi-square, and one-way ANOVA. Results: The mean depression score was 12.17 ± 8. The total MRS mean in this study is 13.04 ± 8.01. The somatic dimension had the highest score, the mean of which was 5.48 ± 3.28. We found a significant relationship between depression score and MRS scores in all three dimensions (P < 0.001). The results did not show any correlation of depression score with mean age, age of menopause, body mass index, waist circumference, or waist-to-hip ratio (P > 0.05). However, the level of education was significantly associated with depression (P < 0.001). Conclusions: Increase in menopausal symptoms is associated with a higher severity of depression. Diagnosis and treatment of menopausal symptoms is therefore recommended to reduce depression.