Recent reports that hyperbaric oxygenation (HBO2) induced apoptosis in T-cell lines raised concern about a possible immunosuppressive effect of HBO2. Nucleosomes, DNA fragments wrapped around a histone core, have been observed in the circulation in diseases with increased cell death such as sepsis. Our aim was to investigate, whether HBO2 increases circulating nucleosomes as a marker of cell death and induces apoptosis of peripheral blood mononuclear cells in vivo. After informed consent 29 healthy volunteers were exposed to a 30 minute dive at 2.8 atmospheres absolute in a pressure chamber under resting conditions, while breathing 100% oxygen. Samples were obtained before and 24 hours after exposure. Circulating nucleosomes were measured in serum. Caspase-3 activation, Bcl-2 expression and mRNA of Bcl-2, Bcl-xl and Bax were analyzed in mononuclear cell extracts. Nucleosomes were elevated markedly 24h after exposure (p<0.01), while caspase-3 was not activated significantly. mRNA levels of Bcl-2, Bcl-xl and Bax were not altered. In conclusion, while evidence of elevated levels of circulating nucleosomes was found, mononuclear cell apoptosis was not affected by a single exposure to hyperbaric oxygen.