Summary Oxycodone’s respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri‐operative period. We randomly assigned ASA 1‐2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg−1, or oxycodone 0.05 mg.kg−1, 0.1 mg.kg−1, or 0.2 mg.kg−1. Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg−1, oxycodone 0.05 mg.kg−1 and 0.1 mg.kg−1, and from 10 patients who received oxycodone 0.2 mg.kg−1. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p < 0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine.