We have previously found that skeletal muscle becomes electrically inexcitable in septic patients. Work in an animal model suggests that a decrease in the available sodium current underlies the loss of electrical excitability. We examined ECGs from patients during periods of septic shock to determine whether there were any ECG abnormalities that might suggest a similar loss of excitability in cardiac tissue during sepsis. Fourteen out of 17 patients had low or significantly decreased QRS amplitudes during septic shock; 8 of 17 had long or increased QRS duration with or without bundle branch block. The mean decrease in QRS amplitude in septic patients was 41%, significantly higher than in controls where no consistent decrease in QRS amplitude was found (p < 0.01). In patients who recovered from septic shock, the QRS amplitude and the increased QRS duration both returned to normal. We conclude that there is a loss of QRS amplitude during septic shock that may be due to altered cardiac excitability.