Background:Infertility is a major stressor for women, influenced by healthcare access, social stigma, and support systems. This study compares stress levels, coping strategies, and quality of life between infertile women in rural and urban Salem.Objectives:To assess stress levels, coping mechanisms, and quality of life among infertile women in rural and urban areas and to explore challenges and coping effectiveness in these regions.Methods:A cross-sectional study was conducted among 125 infertile women from rural and urban Salem attending fertility clinics. Convenience sampling was used, and data were collected via the Depression Anxiety Stress Scale (DASS-21), Coping Inventory for Stressful Situations (CISS), and WHOQOL-BREF quality of life scale. Statistical analysis was performed using the trial version of IBM, SPSS-16.Results:Significant differences were found between rural and urban women. There was a significant association between area (urban vs rural) and physical health (chi(2 )= 67.862, df = 3, P < 0.001). Urban participants generally reported better physical health than rural participants. A significant association was found between area and psychological health (chi(2)= 46.645, df = 3, P < 0.001), with urban participants showing better psychological health compared to their rural counterparts. A strong association was found between area and social relationships (chi(2)= 99.885, df = 2, P < 0.001). Urban participants reported better social relationships, while rural participants reported lower levels of social support. Significant differences in environmental health were also observed between urban and rural participants (chi(2)= 74.523, df = 2, P < 0.001).Conclusions:This study highlights disparities in mental health outcomes and coping effectiveness between rural and urban infertile women. Urban women benefit from better healthcare and support, whereas rural women face challenges with healthcare access and coping strategies. Targeted interventions are needed to improve healthcare and psychological support for rural populations to reduce the emotional burden of infertility.