The presentation of septic patients with low C-reactive protein (CRP) concentrations to the emergency room (ER) might convey an erroneous impression regarding the severity of the disease.We analyzed a retrospective study of septic patients admitted to the internal medicine departments of a relatively large tertiary medical center, following admission to the ER. These patients had CRP concentrations of <31.9 mg/L, the determined cut-off for CRP concentrations in a large cohort of apparently healthy individuals in the community (n = 17,214, upper limit of mean + 3 standard deviations).By processing the electronic medical records, we found 2724 patients with a diagnosis of sepsis, 476 of whom had an admission CRP concentration of <31.9 mg/L. Following further analysis of these records, we found that 34 of the 175 patients (19.4%) who fulfilled the definition of sepsis, died within 1 week of hospitalization. Of special interest was the finding that within <24 h, a significant increment from a median CRP of 16.1 mg/L (IQR 7.9-22.5) to 58.6 mg/L (IQR 24.2-134.4), (P < .001) was noted, accompanied by a velocity change from 0.4 ± 0.29 to 8.3 ± 24.2 mg/L/h following antibiotic administration (P < .001).ER physicians should take into consideration that septic patients with a high in-hospital mortality rate can present with CRP concentrations that are within the range observed in apparently healthy individuals in the community. A second CRP test obtained within 24 h following antibiotic administration might influence attitudes regarding the severity of the disease.