Purpose To investigate the ventilatory response to CO2 in hyperoxia, hypoxia, and during exercise amongst experienced scuba divers and matched controls. Methods Two studies were performed. The first investigated the CO2 sensitivity in rest and exercise using CO2 rebreathing in hyperoxia at a workload typical for diving with divers (n = 11) and controls (n = 11). The second study examined the respiratory drive of divers (n = 10) and controls (n = 10) whilst breathing four different gas mixtures balanced with N2 (ambient air; 25% O2/6% CO2; 13% O2; 13% O2/6% CO2) to assess the combined response to hypercapnia and moderate hypoxia. Results Exercise at a load typical for diving was found to have no effect on the ventilatory sensitivity to CO2 in divers (rest: 1.49 ± 0.33; exercise: 1.22 ± 0.55 [l/min × mmHg−1]) and controls (rest: 2.08 ± 0.71; exercise: 2.05 ± 0.98 [l/min × mmHg−1]) while differences in sensitivity remained between the groups. Inhalation of the four gas mixtures revealed the tested oxygen pressures caused no significant alteration in the ventilatory sensitivity to CO2 in divers and controls. Conclusions Experienced divers possess a lower ventilatory response to CO2 which was not affected by exercise or the tested oxygen pressures suggesting a dominant adaptation of central CO2 sensitivity.