Abstract Background This paper proposes a methodology for helping bridge the gap between the complex waveform information frequently available in an intensive care unit and the simple, lumped values favoured for rapid clinical diagnosis and management. This methodology employs a simple waveform contour analysis approach to compare aortic, femoral and central venous pressure waveforms on a beat-by-beat basis and extract lumped metrics pertaining to the pressure drop and pressure-pulse amplitude attenuation as blood passes through the various sections of systemic circulation. Results Validation encompasses a comparison between novel metrics and well-known, analogous clinical metrics such as mean arterial and venous pressures, across an animal model of induced sepsis. The novel metric O fe → vc , the direct pressure offset between the femoral artery and vena cava, and the clinical metric, ΔMP, the difference between mean arterial and venous pressure, performed well. However, O fe → vc reduced the optimal average time to sepsis detection after endotoxin infusion from 46.2 min for ΔMP to 11.6 min, for a slight increase in false positive rate from 1.8 to 6.2%. Thus, the novel O fe → vc provided the best combination of specificity and sensitivity, assuming an equal weighting to both, of the metrics assessed. Conclusions Overall, the potential of these novel metrics in the detection of diagnostic shifts in physiological behaviour, here driven by sepsis, is demonstrated.