Researchers have speculated that hyperbaric oxygen (HBO) therapy has an antiviral effect in HIV infection. To determine HBO's antiviral effect, the authors performed ex vivo and in vivo quantitative assays on HIV-infected plasma and peripheral blood mononuclear cells (PBMCs) at baseline and after treatment. The authors also HBO-treated uninfected PBMCs and then exposed them to HIV at ambient pressure. HIV viral load was decreased in the infected cells, and few viruses entered uninfected PBMCs exposed to HBO. The results of this study support the theory that HBO has an antiviral effect.