Exhaustion, a consequence of prolonged stress characterized by unusual fatigue, is associated with increased risk of cardiac morbidity and mortality. In patients recovering from coronary artery bypass (CABG), little is known about the relationship of 1) immune-mediated inflammation and resultant endothelial activation, and 2) cumulative exposure to infectious pathogens (pathogen burden (PB)) implicated in coronary atherosclerosis to exhaustion.The aim of this exploratory study was to investigate the association of PB, inflammatory markers (interleukin (IL)-6, IL-10) and a marker of endothelial activation (soluble intercellular adhesion molecule-1 (sICAM-1)) to exhaustion.One to two months post-CABG, 42 individuals who met inclusion criteria were assessed for exhaustion using the Maastricht Interview for Vital Exhaustion. Serum IgG antibodies to herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus, Epstein Barr virus, and inflammatory and endothelial activation markers were measured by enzyme-linked immunosorbent assay. Pathogen burden was defined as the total number of seropositive exposures: low (0-1), moderate (2-3), and high (4).Prevalence of exhaustion was 40.5%. Relative to non-exhausted patients, exhausted patients demonstrated a higher frequency of moderate PB (h=0.73, p=0.04) but lower frequency of high PB (h=1.05, p=0.03). Exhaustion showed a non-significant trend for positive correlations with IL-6 and sICAM-1 levels, and inverse relation to PB. In subgroup analysis, exhausted patients had stronger correlations with IL-6 and IL-6:IL-10 and a tendency towards higher serum IL-10 concentrations compared with their non-exhausted counterparts.This hypothesis-generating study provides preliminary evidence that elevated post-CABG exhaustion may be associated with PB, inflammation, and endothelial activation.