Sublingual and intestinal mucosal blood flow and PCO₂ were studied in a canine model of endotoxin-induced circulatory shock and resuscitation. Sublingual PCO₂ was measured using a novel fluorescent optrode-based technique (P_sCO₂) and compared to lingual measurements obtained using a Stowe-Severinghaus electrode (P_lCO₂). Endotoxin caused parallel changes in cardiac output (Q_t), and in portal, intestinal mucosal (Q_i) and sublingual (Q_s) blood flow. Different blood flow patterns were observed during resuscitation: Q_i returned to near baseline levels post-fluid resuscitation and decreased by 21% after vasopressor resuscitation, whereas Q_s rose to twice that of the pre-shock level and was maintained throughout the resuscitation period. Electrochemical and fluorescent PCO₂ measurements showed similar changes throughout the experiments. The shock-induced increases in P_sCO₂ and P_lCO₂ were nearly reversed after fluid resuscitation despite persistent systemic arterial hypotension. Vasopressor administration induced a rebound of P_sCO₂ and P_lCO₂ to shock levels in spite of higher Q_t and Q_s, possibly due to blood flow redistribution and shunting. Changes in P_lCO₂ and P_sCO₂ paralleled gastric and intestinal PCO₂ changes during shock but not during resuscitation. We found that the lingual, splanchnic, and systemic circulations follow a similar pattern of blood flow variations in response to endotoxin shock, although discrepancies were observed during resuscitation. Restoration of systemic, splanchnic, and lingual perfusion can be accompanied by persistent tissue hypercarbia, mainly lingual and intestinal, more so when a vasopressor agent is used to normalize systemic hemodynamic variables.