Objective: Devices for Automated Oxygen Administration (AOA) have been developed to optimize the therapeutic benefit of oxygen supplementation. We aimed to investigate the effect of AOA on multidimensional aspects of dyspnea and as-needed consumption of opioids and benzodiazepines, as opposed to conventional oxygen therapy, in hospitalized patients with Acute Exacerbation of COPD (AECOPD). Method and Patients: A multicenter randomized controlled trial across five respiratory wards in the Capital Region of Denmark. Patients admitted with AECOPD (n=157) were allocated 1:1 to either AOA (O2matic Ltd), a closed loop device automatically delivering oxygen according to the patient’s peripheral oxygen saturation (SpO₂), or conventional nurse-administered oxygen therapy. Oxygen flows and SpO₂ levels were measured by the O2matic device in both groups, while dyspnea, anxiety, depression, and COPD symptoms were accessed by Patient Reported Outcomes. Results: Of the 157 randomized patients, 127 had complete data for the intervention. The AOA reduced patients’ perception of overall unpleasantness significantly on the Multidimensional Dyspnea Profile (MDP) with a difference in medians of −3 (p=0.003) between the intervention group (n=64) and the control group (n=63). The AOA also provided a significant between group difference in all single items within the sensory domain of the MDP (all p-values≤0.05) as well as in the Visual Analogue Scale – Dyspnea (VAS-D) within the past three days (p=0.013). All between group differences exceeded the Minimal Clinical Important Difference of the MDP and VAS-D, respectively. AOA did not seem to have an impact on the emotional response domain of the MDP, the COPD Assessment Test, the Hospital Anxiety and Depression Scale, or use of as-needed opioids and/or benzodiazepines (all p-values>0.05). Conclusion: AOA reduces both breathing discomfort and physical perception of dyspnea in patients admitted with AECOPD but did not seem to impact the emotional status or other COPD symptoms.