Purpose: To examine the association of seizures with health‐related quality of life (HRQOL), physical and psychiatric comorbidities, and health behaviors. Methods: We analyzed data obtained from adults aged 18 years or older (n = 30,445) who participated in the 2002 National Health Interview Survey, an ongoing, computer‐assisted personal interview of the noninstitutionalized U.S. population. Results: An estimated 1.4% of adults 18 years or older reported being told by a health care professional that they had seizures. Persons with seizures were significantly more likely than those without seizures to report lower levels of education, higher levels of unemployment, pain, hypersomnia and insomnia, and psychological distress (e.g., feelings of sadness, nervousness, hopelessness, and worthlessness). In addition, they were significantly more likely to report insufficient leisure‐time physical activity as well as physical comorbidities such as cancer, arthritis, heart disease, stroke, asthma, severe headaches, lower back pain, and neck pain. Conclusions: Our findings suggest that it is advisable for health care professionals to assess psychiatric and physical comorbidities among patients with a history of seizures potentially to improve patient health outcomes. Furthermore, public health surveillance systems should include questions on seizures, epilepsy, and mental health to better examine associations among these disorders and to better identify populations meriting further assessment and intervention.