The aim of this study was to assess the value of parameters of tissue oxygenation in monitoring the progression to irreversibility in a quantitative model of hemorrhagic shock. Rats were bled to a mean arterial pressure of 40 mmHg and were maintained at this level by further blood withdrawal until the compensation endpoint; this point was defined as the time at which the rat was no longer able to maintain its blood pressure at this level and shed blood was required for transfusion. The shock period was maintained until 0%, 20%, 40%, or 50% of the maximum shed blood volume (MBV) had been returned (n = 10 in each group, total n = 40). The animals were then resuscitated with remaining shed blood plus twice MBV as lactated Ringer's solution to MAP > 80 mmHg. Blood gas and serum lactate samples were measured at baseline, compensation endpoint, and at the time of resuscitation, and 24 h survival was recorded. Increasing the severity of shock progressively worsened the acidosis, with increased base deficit and lacticacidemia, and deterioration in central venous oxygen saturation (Cvo2). Tissue oxygenation parameters, particularly Cvo2, predicted subsequent mortality. Lactate levels only predicted irreversibility in late, severe shock. This quantitative model of hemorrhagic shock showed that tissue oxygenation parameters can be used to monitor the progression from the decompensated phase of hemorrhagic shock to irreversibility. Furthermore, this experimental study suggests that venous indices may be a valuable tool in reflecting the severity of hemorrhagic insult in a setting when arterial blood samples may not be easily available.