Objective <p>People with serious mental illness (SMI) face higher morbidity and mortality due to cardiovascular disease (CVD). Low health literacy (HL) is a risk factor for CVD, but the relationship between HL and CVD is understudied in people with SMI. This study examined the association between HL and (1) prevalence of metabolic syndrome (MetS) and (2) risk and prevalence of CVD in people with SMI.</p> Methods <p>Participants with diagnosed SMI were enrolled in this cross-sectional study at a behavioral health agency (<i>N</i> = 140). HL was measured using the Health Literacy Questionnaire (HLQ) and participants were categorized by low, moderate, or high HL. MetS was determined by National Cholesterol Education Program’s Adult Treatment Panel (NCEP ATP) III criteria. CVD risk was calculated using the Framingham 10-year risk score. Prevalent CVD included self-reported history of myocardial infarction, congestive heart failure, and/or other heart disease.</p> Results <p>Most participants identified as Black (61%) and male (64%) with education levels varying from less than high school to some college or more. In multivariable models, low HL was associated with increased prevalence of MetS (<i>p</i> = 0.013), risk of CVD (<i>p</i> = 0.030), and prevalence of CVD (<i>p</i> = 0.037) after adjusting for age, gender, race, ethnicity, education, nicotine dependence, and depression, anxiety, and stress symptoms.</p> Conclusions and Implications for Practice <p>Low HL is associated with poorer cardiometabolic health in people with SMI. Prospective studies adequately powered to examine the relationships between HL, MetS, and CVD in this population are warranted.</p>