Despite widespread tcPCO2 monitoring the relationship between tcPCO2 and PaCO2 remains unclear. It has been assumed that after standard temperature correction, a constant metabolic factor can explain the elevation of tcPCO2 over PaCO2. Our data demonstrate a progressive increase in the difference between temperature corrected tcPCO2 and PaCO2 as PaCO2 increases. Thus a constant metabolic factor cannot account for the elevation of temperature corrected tcPCO2 over PaCO2. We speculate that as PaCO2 rises, CO2 production exceeds removal resulting in a progressive gradient between temperature corrected tcPCO2 and PaCO2.