Pakistan along with many other West and South Asian countries has a very high prevalence of consanguineous, especially close cousin, marriages. Although there is substantial empirical information on offspring morbidity and mortality attributable to parental consanguinity, population-based information on how communities in general, and women in particular, perceive the health risks associated with consanguineous unions is limited. This paper considers community perceptions of health effects associated with consanguineous marriages using qualitative data from 15 focus group discussions and 294 in-depth interviews. The study was conducted in four low-income, multi-ethnic, and multi-religious communities in Karachi, the principal commercial center of Pakistan. The results show a general lack of awareness of the possible adverse health effects of consanguineous marriage. In cases where a link between consanguinity and ill health was acknowledged, it often centered on the familial origins of non-communicable disorders such as diabetes and hypertension or infectious diseases such as tuberculosis. Belief in fate and the “evil eye” was widespread across all ethnic and religious groups. Many respondents did not agree with medical explanations of a genetic mode of disease inheritance, even in cases where there was an affected child in the family. The absence of a uniform manifestation of disease among all children of a couple who were identified as carriers of a specific mutation added to the confusion among participants. The study highlights the need for further quantification of risks associated with consanguinity and a need for provision of appropriate information to primary-care clinicians and also to communities. The likely impact of increasing morbidity attributable to inbreeding on the health care system in resource poor settings is also discussed