The normal heart rate is regulated by a number of interacting physiological control systems that operate on widely different time scales. Thus, instantaneous heart rate is not steady, but rather demonstrates continuous fluctuations. It has been recognized that power spectral analysis of heart rate variability (HRV) is a noninvasive method to assess cardiac autonomic modulation. We hypothesized that the loss of interconnectivity or coupling between heart and other organs results in the occurrence of septic shock in patients with severe sepsis. We found that the reduction of HRV precedes the occurrence of septic shock. Therefore, we conclude that analysis of HRV is a novel and useful tool to predict the occurrence of septic shock among the patients with severe sepsis.