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Clinical trials have shown that mild hyperthermia (HT) serves as an adjunct to cancer treatments such as chemo- and radiotherapy. Recently, a high efficacy of mild HT immediately followed by hypofractionated radiotherapy (RT) in treatment of recurrent breast cancer has been documented if temperatures of 39-43 °C are achieved for 40-60 min. In the present study, temperature and oxygenation profiles were measured in superficial tissues of healthy volunteers exposed to water-filtered infrared-A- (wIRA)- irradiation, to verify that adequate thermal doses together with the improved tumor oxygenation necessary for radiosensitisation are obtained. Experiments were performed using a wIRA-system equipped with two wIRA-radiators, each with a thermography camera for real-time monitoring of the skin surface temperature. Temperatures within the abdominal wall were measured with fibre optic sensors at defined tissue depths (subepidermal, and 1-20 mm inside the tissue). The corresponding tissue pO 2 values were assessed with fluorometric microsensors. In selected situations, hyperspectral tissue imaging was used to visualise the oxygenation status of normal skin and superficial tumours in patients. Pre-treatment skin surface temperature was 34.6 °C. Upon wIRA exposure, average skin surface temperatures reached 41.6 °C within 5-12 min. Maximum tissue temperatures of 41.8 °C were found at a tissue depth of 1 mm, with a steady decline in deeper tissue layers (41.6 °C @ 5 mm, 40.8 °C @ 10 mm, 40.6 °C @ 15 mm, and 40.1 °C @ 20 mm). Effective HT levels ≥39 °C were established in tissue depths up to 25 mm. Tissue heating was accompanied by a significant increase in tissue pO 2 values [e.g., at a tissue depth of 13 mm mean pO 2 rose from 46 mmHg to 81 mmHg (@ T = 40.5 °C). In the post-heating phase (+ 5 min), pO 2 was 79 mmHg (@ T = 38 °C) and 15 min post-heat pO 2 was 72 mmHg (@ T = 36.8 °C)]. pO 2 values remained elevated for 30-60 min post-heat. Non-invasive monitoring of normal skin and of recurrent breast cancers confirmed the improved O 2 status by wIRA-HT. In conclusion, wIRA-irradiation enables effective tissue heating (T = 39-43 °C) associated with distinct increases in blood flow and pO 2 . These adjustments unequivocally meet the requirement for effective radiosensitisation., (© 2022. Springer Nature Switzerland AG.)