Background and AimOn a global scale, an estimated 17.5% of the reproductive‐aged population experiences clinical infertility. Beyond its categorization as a reproductive health concern, infertility emerges as a substantial independent risk factor for the development of various mental health disorders. The current study aims to investigate the prevalence of depression among women experiencing infertility compared to fertile women in Herat city, Afghanistan.MethodsThis hospital‐based case‐control study was conducted in Herat city, Afghanistan, during the latter half of 2023 on women aged 15–49. Sociodemographic and infertility data were gathered by a gynecologist using a structured questionnaire with 14 items. Assessment of depression employed the Dari‐translated version of the Patient Health Questionnaire. The data were scored and categorized following the instrument's guidelines. To examine the association between categorical variables, a chi‐square test was conducted, with a significance level set at 0.05 for all analyses. These statistical procedures were performed using IBM Statistical Package for Social Sciences, version 27.ResultsOur investigation revealed a statistically significant association (p < 0.001) between infertility and depression. Infertility was associated with a markedly increased risk of depression, as evidenced by a prevalence of 79.0% in infertile women compared to 44.4% in fertile women. The study found a link between depression, health, and nutritional status in both infertile and fertile participants. Notably, within the infertile group, the longer a woman struggled with infertility, the more likely she was to experience depression.ConclusionGiven the substantial prevalence and important correlates of depression among infertile women in Herat, Afghanistan, it is imperative for policymakers, mental health professionals, and gynecologists to specifically address the mental well‐being of this vulnerable population.