Background: Patients with Chronic Obstructive Pulmonary Disease (COPD) who received supplemental oxygen reported improved symptoms such as increased energy, less breathlessness, and improved quality of life, even though the oxygen therapy was not actually providing any additional therapeutic benefit beyond maintaining adequate oxygen levels. Aims and objectives: To investigate the impact of the placebo effect on oxygen therapy during the 6-Minute Walking Test (6MWT) in patients with COPD. Methods: A randomized crossover two-arm study was conducted with 95 patients with COPD (68.4% male, average age 67). All participants underwent baseline assessments, including the Mini-Mental Status Examination, the Modified British Medical Research Council Questionnaire, the Fatigue Severity Scale, and Simple Spirometry. All participants underwent 6MWT, using one medical oxygen (O2) concentrator and another whose molecular filters (MF) had been removed, so patients believed the concentrator was delivering oxygen. The sequence of the first group was ABC (A = Baseline, B =MF, C = O2), while the sequence of the second was ACB. Saturation, heart rate and blood pressure were measured at baseline, at 3?:30?? and after 6MWT. Results: A repeated measures ANOVA was performed to compare the effect of oxygen usage on the 6MWT. There was no statistically significant difference in the 6MWT between the two groups (F(2, 1) = 0.113, p = 0.888). Conclusions: Although the use of oxygen remains an important and effective treatment for maintaining adequate oxygen levels, specific treatments based on beliefs and patients' expectations can improve the healthcare process in COPD.