Savannah monitor lizards (Varanus exanthematicus) are unusual among ectothermic vertebrates in maintaining arterial pH nearly constant during changes in body temperature in contrast to the typical α-stat regulating strategy of most other ectotherms. Given the importance of pH in the control of ventilation, we examined the CO 2 /H + sensitivity of neurons from the locus coeruleus (LC) region of monitor lizard brainstems. Whole-cell patch-clamp electrophysiology was used to record membrane voltage in LC neurons in brainstem slices. Artificial cerebral spinal fluid equilibrated with 80% O 2 , 0.0-10.0% CO 2 , balance N 2 , was superfused across brainstem slices. Changes in firing rate of LC neurons were calculated from action potential recordings to quantify the chemosensitive response to hypercapnic acidosis. Our results demonstrate that the LC brainstem region contains neurons that can be excited or inhibited by, and/or are not sensitive to CO 2 in V. exanthematicus. While few LC neurons were activated by hypercapnic acidosis (15%), a higher proportion of the LC neurons responded by decreasing their firing rate during exposure to high CO 2 at 20°C (37%); this chemosensitive response was no longer exhibited when the temperature was increased to 30°C. Further, the proportion of chemosensitive LC neurons changed at 35°C with a reduction in CO 2 -inhibited (11%) neurons and an increase in CO 2 -activated (35%) neurons. Expressing a high proportion of inhibited neurons at low temperature may provide insights into mechanisms underlying the temperature-dependent pH-stat regulatory strategy of savannah monitor lizards.