There is a constant concern about finding new or alternative therapeutical approaches for symptom control and quality of life that are essential in palliative care. Ozone therapy has been studied for over a century, since the development of the first medical ozone-generator able to ensure a correct titration of the ozone-oxygen mixture. When used in precise therapeutic doses O3 prove many consistent and safe therapeutic benefits, with minimal and preventable side actions. Our prospective exploratory study aimed to analyze the effects of ozone therapy administration on palliative care patients, by dynamically monitoring the antioxidant status (superoxide-dismutase and glutathione-peroxidase serum levels), pain perception, and quality of life. The results confirm ozone therapy as a promising alternative adjuvant therapy for increasing the quality of life in palliative care services.