An 8-year-old, 167 kg mule was scheduled for surgical treatment of a hip luxation in lateral recumbency. During general anaesthesia, after a short phase of spontaneous breathing followed by mechanical ventilation at standard settings, the mule developed hypoxaemia (arterial oxygen partial pressure (PaO 2 ) 8.3 kPa). First, respiratory rate, tidal volume and fraction of inspired oxygen (FiO 2 ) were increased; 5 cmH 2 0 of positive end-expiratory pressure (PEEP) and nebulized salbutamol were administered. Second, three vital capacity manoeuvres were executed (tidal volume of 20 ml kg −1 ). No immediate improvement in PaO 2 (8.0 kPa) was observed. A further recruitment manoeuvre with increased peak inspiratory pressure (up to 44 cmH 2 O) and PEEP (25 cmH 2 O) was performed. Over the following 120 min, PaO 2 increased progressively. The mule recovered without complications. This case reports that mules can develop hypoxaemia during general anaesthesia that can be treated with recruitment manoeuvres. However, the effect may not be immediate.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.