INTRODUCTION: This study evaluates the utility of heart rate variability (HRV) for assessment of severity of illness and poor outcome in Emergency Department (ED) patients with sepsis. HRV measures evaluated included low frequency (LF) signal, high frequency (HF) signal, and deviations in LF and HF signal from age-adjusted reference values. METHODS: This was a prospective, observational study. Seventy-two adult ED patients were assessed within 6 h of arrival. RESULTS: Severity of illness as defined by sepsis subtype correlated with decreased LF signal (sepsis: 70.68 +/- 22.95, severe sepsis: 54.00 +/- 28.41, septic shock: 45.54 +/- 23.31, p = 0.02), increased HF signal (sepsis: 27.87 +/- 19.42, severe sepsis: 44.63 +/- 27.29, septic shock: 47.66 +/- 20.98, p = 0.01), increasingly negative deviations in LF signal (sepsis: 0.41 +/- 24.53, severe sepsis: -21.43 +/- 30.09, septic shock -30.39 +/- 26.09, p = 0.005) and increasingly positive deviations in HF signal (sepsis: -1.86 +/- 21.09, severe sepsis: 20.07 +/- 29.03, septic shock: 23.6 +/- 24.17, p = 0.004). Composite poor outcome correlated with decreased LF signal (p = 0.008), increased HF signal (p = 0.03), large negative deviations in LF signal (p = 0.004) and large positive deviations in HF signal (p = 0.02). Deviations in LF and HF signal from age-adjusted reference values correlated with individual measures of poor outcome with greater consistency than LF or HF signal. DISCUSSION: Accounting for the influence of age on baseline HRV signal improves the predictive value of HRV measures in ED patients with sepsis.