Whereas some research suggests that acknowledgment of the role of biogenetic factors in mental illness could reduce mental illness stigma by diminishing perceived responsibility, other research has cautioned that emphasizing biogenetic aspects of mental illness could produce the impression that mental illness is a stable, intrinsic aspect of a person ("genetic essentialism"), increasing the desire for social distance. We assessed genetic and neurobiological causal attributions about mental illness among 85 people with serious mental illness and 50 members of the public. The perceived responsibility of persons with mental illness for their condition, as well as fear and social distance, was assessed by self-report. Automatic associations between Mental Illness and Guilt and between Self and Guilt were measured by the Brief Implicit Association Test. Among the general public, endorsement of biogenetic models was associated with not only less perceived responsibility, but also greater social distance. Among people with mental illness, endorsement of genetic models had only negative correlates: greater explicit fear and stronger implicit self-guilt associations. Genetic models may have unexpected negative consequences for implicit self-concept and explicit attitudes of people with serious mental illness. An exclusive focus on genetic models may therefore be problematic for clinical practice and anti-stigma initiatives.