<p>Hyperbaric Oxygenation Therapy (HBOT) is a widely used therapeutic option. It involves cycles with administration of 100% oxygen at increased atmospheric pressure to enhance oxygen delivery to tissues. The application of HBOT may affect all organs and tissues including kidneys which may be sensitive to the changes during HBOT. As underlying mechanisms for HBOT, the production of reactive oxygen species including superoxide, antioxidant reactions, increased plasma levels of growth factors and nuclear hypoxia-inducible factor-1α (HIF-1α) expression are discussed. Although HBOT is frequently used in man, knowledge about effects of HBOT on kidney function is still lacking in humans. The aim of this pilot study was to monitor changes in renal function parameters, including hypoxia inducible factor 1α (HIF-1α) and erythropoietin and employing urinary EV´s to document renal alterations. Test persons (<i>n</i> = 23) enrolled presented healthy renal status and received 10 HBOT sessions. Blood and urine samples were taken at the first, the fifth and the tenth HBOT session. Heart rate decreased during HBOT in male and female test persons which may be due to a stimulation of vagal nerve activity. Serum HIF-1α and erythropoietin values, blood pressure, blood and urine values for renal function parameter except for urine osmolality remained unaffected by HBOT. Urine osmolality together with the trend of renal Na⁺/K⁺/2Cl⁻-cotransporter expression on isolated urinary extracellular vesicles during HBOT significantly increased in both female in male test persons. Most likely, the generation of superoxide may account for the trend in the augmented renal NKCC2 expression and urine osmolality. HIF-1α downstream targets including renal sodium transporter affected by HIF-1α alteration remained unchanged suggesting the relative hypoxia after end of HBOT may not be sufficient. Overall, renal function upon HBOT remained largely unaffected with only minor alterations in urine osmolality.</p>