Modic changes (MCs) have attracted great interest in recent years. The complex process of MC development and progression seems to involve interplay between mechanical, infective, inflammatory, and degenerative processes that cannot be clearly differentiated. Based on signal intensity on T1- and T2-weighted MRI scans, MCs can be divided three types: Type 1, Type 2, and Type 3. Predominantly Type 1 MCs are commonly associated with chronic low back pain that is unresponsive to classic treatment options. Infection with low-virulent anaerobic microorganisms, most commonly Propionibacterium acnes, has been implicated in MC development following a disc herniation when a tear enables bacteria to enter the disc. Recent studies in patients with chronic low back pain following a lumbar disc herniation associated with Type 1 MCs have reported promising results following prolonged systemic antibiotic treatment with amoxicillin-clavulanate. Hyperbaric oxygen therapy, as primary or adjuvant treatment in association combination with systemic antibiotics or anti- inflammatory therapy, could offer important advantages in treating patients with suspected low- virulent disc infections due to anaerobic microorganisms associated with Type 1 MCs. We believe that hyperbaric oxygenation could contribute to faster resolution of Type 1 MCs and associated pain through multiple effects—including direct antimicrobial effects through formation of reactive oxygen species (ROS), altering the favorable low oxygen tension milieu such that it becomes unfavorable for bacterial growth and survival, and anti-biofilm effects. Additionally, hyperbaric oxygenation could contribute to faster pain resolution via direct and indirect anti-inflammatory effects. As an adjuvant treatment administered in combination with systemic antibiotics, HBOT could increase the sensitivity of Propionibacterium acnes to antimicrobial drugs under hyperoxic conditions, resulting in faster MC resolution. Overall, the faster infection resolution, diminished bacterial load, and anti-inflammatory effects due to reduced cytokine expression and levels of infectious by- products could lead to faster pain resolution following HBOT, and a significant improvement of quality of life in these patients.