Despite the introduction of new inflammatory markers, C-reactive protein (CRP) remains commonly used in patients hospitalised with severe infections. However, evidence on the usefulness of consecutive CRP measurements is still unclear. The clinical relevance of consecutive CRP measurements was studied in follow-up of antibiotic treatment in patients with severe community-acquired pneumonia (CAP). In a prospective multicentre trial, CRP levels were measured on admission, and on days 3 and 7. Patients were followed clinically for 28 days. Aetiology could be determined in 137 (47.4%) out of the 289 patients included. In 122 (38.8%) patients, initial antibiotic therapy was appropriate. A decline of <60% in CRP levels in 3 days and a decline of <90% in CRP levels in 7 days were both associated with an increased risk of having received inappropriate empiric antibiotic treatment (day 0-3, odds ratio (OR) 6.98, 95% confidence interval (CI) 1.56-31.33 and day 0-7, OR 3.74, 95% CI 1.12-13.77). In conclusion, consecutive C-reactive protein measurements are useful in the first week in follow-up of antibiotic treatment for severe community-acquired pneumonia when taking the causative microorganism and use of steroids into account. A delayed normalisation of C-reactive protein levels is associated with a higher risk of having received inappropriate antibiotic treatment.