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Objective: Cognitive deficits are common in patients with heart failure (HF), and can negatively affect self-care, predict rehospitalizations, and increase mortality rates 5-fold. Inflammation can produce vascular pathology, reducing cerebral blood flow to brain regions necessary for optimal cognitive function. The purpose of the investigation was to identify a pattern of peripheral blood inflammation-related biomarkers associated with cognitive impairment in patients with HF. Methods: Forty-five outpatients (median age = 67 years, SD = 9.9) were recruited from University of California, San Diego (UCSD) and Veterans Affairs San Diego Healthcare Systems (VASDHS), diagnosed with New York Heart Association Stages I–III HF. Participants were administered the Montreal Cognitive Assessment (MoCA) as a measure of global cognitive impairment, and blood was analyzed for plasma biomarkers, interferon-γ, tumor necrosis factor-α (TNFα), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), brain-derived neurotrophic factor (BDNF), interleukin-8 (IL-8), matrix metallopeptidase-9 (MMP-9), IL-6, C-reactive protein (CRP), and serum amyloid-A (SAA). Results: Almost half the patients scored below the threshold on the MoCA, indicating at least mild cognitive impairment. A factor analysis produced three biomarker factors: vascular inflammatory factor-1: TNFα, sICAM1, sVCAM1; neuroinflammatory factor-2: BDNF, MMP-9, IL-8; peripheral inflammatory factor-3: IL-6, CRP, SAA. Only vascular inflammatory factor-1 was significantly associated with cognitive function (MoCA) (ΔR2 = 0.214, beta = –0.468, p = 0.008). Conclusions: In this cohort with HF, vascular inflammation appears related to poorer cognitive function. This could indicate targets for treatment to reduce cognitive deficits in HF. However, this is a preliminary study, and further research is needed. [ABSTRACT FROM AUTHOR]