Introduction. Hyperbaric oxygen therapy is a treatment option for an increasing number of conditions. The aim of this study was to assess its therapeutic effects in femoral condylar necrosis as well as in normal tissue using hyperspectral imaging. Material and method. A 47-year-old female patient diagnosed with avascular necrosis of the medial femoral condyle was included in this study. The patient received hyperbaric oxygen therapy for two consecutive days (the first day: three stages of 30 min each, separated by two breaks of 5 min at pO2 = 2 ATA; the second day: three stages of 30 min each, separated by two breaks of 5 min at pO2 = 2.4 ATA). The effects of hyperbaric oxygen therapy on the affected area (patient’s knee) and normal (patient’s hand) tissues oxygenation were assessed before and after each treatment session using hyperspectral imaging. Results and discussions. The results showed that hyperspectral imaging is quite good for monitoring the hyperbaric oxygen therapy efficacy in affected areas, even with deep tissue problems. Conclusions. In conclusion, the hyperspectral imaging-based approach for monitoring hyperbaric oxygen therapy could support physicians in extracting prognostic information and making the right treatment decisions.