The responses of estuarine invertebrates to hypoxic conditions are well established. However, many studies have investigated hypoxia as an isolated condition despite its frequent co-occurrence with hypercapnia (elevated CO ). Although many studies suggest deleterious effects, hypercapnia has been observed to improve blue crab walking performance in hypoxia. To investigate the physiological effects of combined hypercapnic hypoxia, we measured Po , pH, [l-lactate], Pco , and total O in pre- and postbranchial hemolymph sampled from blue crabs during walking exercise. Crabs walked at 8 m min on an aquatic treadmill in normoxic (100% air saturation), moderately hypoxic (50%), and severely hypoxic (20%) seawater with and without the addition of hypercapnia (about 2% CO ). Respiration was almost completely aerobic in normoxic conditions, with little buildup of lactate. During exercise under severe hypoxia, lactate increased from 1.4 to 11.0 mM, indicating a heavy reliance on anaerobic respiration. The O saturation of arterial hemocyanin was 47% in severe hypoxia after 120 min, significantly lower than in normoxia (80%). However, the addition of hypercapnia significantly increased the percentage saturation of arterial hemocyanin in severe hypoxia to 92% after 120 min of exercise, equivalent to normoxic levels. Hypercapnia in severe hypoxia also caused a marked increase in hemolymph Pco (around 1.1 kPa), but caused only a minor decrease in pH of 0.1 units. We suggest that the improved O saturation at the gills results from a specific effect of molecular CO on hemocyanin oxygen binding affinity, which works independently of and counter to the effects of decreased pH.