Aim of this study was to assess the therapeutic outcome of CT-guided periganglionic infiltration of oxygen-ozone and injection of the gas mixture into the lysis points in patients with first grade spondylolisthesis and spondylolysis. We selected 18 patients presenting with low back pain and sciatica resistant to physical and medical management with a radiological diagnosis of spondylolisthesis and spondylolysis subsequently confirmed on CT scan. Following CT-guided bilateral periganglionic O2-O3 infiltration and injection into the lysis points, 15 patients (83.3%) obtained a complete remission of pain. None of the patients reported pain recurrence at clinical follow-up visits one, three and six months after treatment. Oxygen-ozone therapy administered in this way is even more effective than CT-guided periganglionic infiltration alone as it has an additional anti-inflammatory and analgesic effect on the nerve structures in the neural arch, namely Luschka's recurrent nerve.