Abstract Aims Plasma concentrations of high-sensitivity C-reactive protein (hsCRP) are often raised in chronic heart failure (CHF) and might indicate inflammatory processes that could be a therapeutic target. We aimed to study the associations between hsCRP, mode and cause of death in patients with CHF. Methods and results We enrolled 4423 patients referred to a heart failure clinic serving a local population. CHF was defined as relevant symptoms or signs with either a reduced left ventricular ejection fraction <40% or raised plasma concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP >125 pg/mL). The median [interquartile range (IQR)] plasma hsCRP for patients diagnosed with CHF (n = 3756) was 3.9 (1.6–8.5) mg/L and 2.7 (1.3–5.1) mg/L for those who were not (n = 667; P < 0.001). Patients with hsCRP ≥10 mg/L (N = 809; 22%) were older and more congested than those with hsCRP <2 mg/L (N = 1117, 30%). During a median follow-up of 53 (IQR 28–93) months, 1784 (48%) patients with CHF died. Higher plasma hsCRP was associated with greater mortality, independent of age, symptom severity, creatinine, and NT-proBNP. Comparing a hsCRP ≥10 mg/L to <2 mg/L, the hazard ratio for all-cause mortality was 2.49 (95% confidence interval 2.19–2.84; P < 0.001), for cardiovascular (CV) mortality was 2.26 (1.91–2.68; P < 0.001), and for non-CV mortality was 2.96 (2.40–3.65; P < 0.001). Conclusion In patients with CHF, a raised plasma hsCRP is associated with more congestion and a worse prognosis. The proportion of deaths that are non-CV also increases with higher hsCRP.