Severe burn results in severe and unique physiological changes called burn shock. Historically, resuscitation has been guided by a combination of basic laboratory values, invasive monitoring and clinical findings, but the optimal guide to the endpoint of resuscitation still remains controversial. Two hundred and eighty patients, who were admitted to our Burn Unit, were enrolled in this prospective study. Resuscitation of these patients was undertaken according to the current standard of care. Parkland formula was used as a first approximation of acquired fluid administration rates; final fluid administration was adapted in order to meet clinical needs. The aim of this study was to evaluate if plasma lactate (PL) and base deficit (BD) are useful early parameters to estimate the severity of a burn. One of the main objectives was to evaluate if BD and its changes due to fluid resuscitation adds additional information in comparison to the evaluation of PL alone. The results of this study indicate that initial PL and BD level (Day 0) are useful parameters to separate survivors from non-survivors. Moreover, an outcome predictor of shock and effective resuscitation could be defined by evaluating the changes of BD on Day 1. Normalization of the BD within 24 h is associated with a better chance of survival. One explanation for this phenomenon might be the fact that many burn patients are still sub-optimally resuscitated; in summary, measuring PL and BD may help to identify critically injured patients either for enhancement of treatment, or selection of therapeutic options.