OBJECTIVES: Identifying sociocultural correlates of neurocognitive dysfunction among Hispanics/Latinos, and their underlying biological pathways, is crucial for understanding disparities in Alzheimer's disease and related dementias. We examined cross-sectional associations between stress and neurocognition, and the role that metabolic syndrome (MetS) and systemic inflammation might play in these associations. METHOD: Participants included 3,045 adults aged 45-75 (56% female, education 0-20+ years, 86% Spanish-speaking, 23% U.S.-born), enrolled in the Hispanic Community Health Study/Study of Latinos and its Sociocultural Ancillary Study. Global neurocognition was the primary outcome and operationalized as the average of the z scores of measures of learning and memory, word fluency, and processing speed. Stress measures included self-report assessments of stress appraisal (perceived and acculturative stress) and exposure to chronic and traumatic stressors. MetS was defined via established criteria including waist circumference, high blood pressure, elevated triglycerides, fasting plasma glucose, and high levels of high-density lipoprotein cholesterol. Systemic inflammation was represented by high-sensitivity C-reactive protein (hs-CRP). RESULTS: Separate survey multivariable linear regression models adjusting for covariates showed that higher perceived (b = -0.004, SE = 0.002, p < .05) and acculturative stress (b = -0.004, SE = 0.001, p < .0001) were significantly associated with worse global neurocognition, while lifetime exposure to traumatic stressors was associated with better global neurocognition (b = 0.034, SE = 0.009, p < .001). Neither MetS nor hs-CRP were notable pathways in the association between stress and neurocognition; rather, they were both independently associated with worse neurocognition in models including stress measures (ps < .05). DISCUSSION: These cross-sectional analyses suggest that stress appraisal, MetS, and systemic inflammation may be targets to reduce neurocognitive dysfunction among Hispanics/Latinos.