The purpose of this study was to observe the interactions between cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), intra-abdominal pressure (IAP) and total circulating blood volume index (TBVI) during resuscitation of major burns. Sixteen patients with an average TBSA of 46% (26-67%) and an average abbreviated burn severity index of 8.9 (7-11) were included into an intra-individual comparative prospective study over an 18-month period. The COLD Z-021 system (Pulsion Medical Systems, Munich, Germany) was used to obtain CI, SVI and TBVI. Two hundred and thirty-four to 278 intra-individually comparative measurements were performed for the analyses during the first 4 days after the burn injury. Correlations were shown for the interactions between CI and TBVI (r = 0.550; rs = 0.518), SVI and TBVI (r = 0.606; rs = 0.626) and for CVP versus IAP (r = 0.487; rs = 0.474). Poor or no correlations were demonstrated for the comparisons CI versus CVP (r = 0.401; rs = 0.352), CVP-PEEP versus IAP (r = 0.255; rs = 0.272). TBVI versus IAP (r = -0.120; rs = -0.169), TBVI versus CVP (r = 0.025; rs = -0.036), TBVI versus CVP-PEEP (r = -0.046; rs = -0.101), CI versus CVP-PEEP (r = 0.088; rs = 0.092) as well as for IAP versus CI (r = 0.050; rs = 0.034). An additional analysis demonstrated no correlation between TBVI and MAP (r = -0.095; rs = -0.136). Our data provide evidence that the CVP is influenced more by external pressures (IAP) than by the actual intravascular volume status of the patient. Thus, the CVP is not a suitable tool to guide fluid resuscitation during burns with shock. The TBVI may be an ideal value to guide resuscitation because the augmentation of TBVI during fluid resuscitation correlated well with improved cardiac output and stroke volume. Future randomised studies are required to demonstrate whether TBVI guided resuscitation of burns has an impact on outcome.