Oxygen is a powerful trigger for cellular reactions, but there are few comparative investigations assessing the effects over a large range of partial pressures. We investigated a metabolic response to single exposures to either normobaric (10%, 15%, 30%, 100%) or hyperbaric (1.4 ATA, 2.5 ATA) oxygen. Forty-eight healthy subjects (32 males/16 females; age: 43.7 ± 13.4 years, height: 172.7 ± 10.07 cm; weight 68.4 ± 15.7 kg) were randomly assigned, and blood samples were taken before and 2 h after each exposure. Microparticles (MPs) expressing proteins specific to different cells were analyzed, including platelets (CD41), neutrophils (CD66b), endothelial cells (CD146), and microglia (TMEM). Phalloidin binding and thrombospondin-1 (TSP), which are related to neutrophil and platelet activation, respectively, were also analyzed. The responses were found to be different and sometimes opposite. Significant elevations were identified for MPs expressing CD41, CD66b, TMEM, and phalloidin binding in all conditions but for 1.4 ATA, which elicited significant decreases. Few changes were found for CD146 and TSP. Regarding OPB, further investigation is needed to fully understand the future applications of such findings.