Pro-inflammatory cytokines and their circulating receptors are powerful predictors of poor outcome in patients with chronic heart failure (CHF). We hypothesized that Type D personality, known to independently predict long-term mortality in patients with coronary heart disease, would relate to immune activation in CHF.91 stable CHF patients (79% males, mean age 57±13 yrs, 58% ischemic heart disease) with left ventricular ejection fraction ≤35% completed a psychological questionnaire to assess Type D personality (i.e., the tendency to experience negative emotions and to inhibit their expression). Plasma levels of tumour necrosis factor (TNF)-α, soluble TNF-α receptor 1 and 2 (sTNFR1 and sTNFR2) and interleukin-6 (IL-6) were measured by ELISA.Type D patients (n=30) had higher levels of TNF-α (5.1±2.9 versus 3.9±2.6 pg/ml, p=0.066), sTNFR1 (1656±1057 versus 1098±424 pg/ml, p=0.009) and sTNFR2 (2869±1510 versus 2011±794 pg/ml, p=0.006) as compared to non-Type D patients (n=61), whereas IL-6 was not different. After controlling for sex, age, ischemic etiology and disease severity, multivariate analysis yielded Type D as the strongest predictor of increased TNF-α (OR=2.9, p=0.048) and sTNFR2 levels (OR=3.9, p=0.018). For sTNFR1, the effect of Type D was no longer significant in this analysis (OR=2.7, p=0.112).Type D personality was independently associated with increased circulating levels of TNF-α and sTNFR2 in patients with CHF. This study provides the strongest evidence to date that chronic emotional distress may be associated with immune activation in heart failure.