Professional and recreational diving are growing activities in modern life. Diving has been associated with increased prevalence of stroke, hypertension, asthma, diabetes, or bone necrosis. We evaluated the effect of increased pressure equivalent to diving at 30 and 60 m for 30 min in two groups of divers using an untargeted approach with LC-MS fingerprinting of plasma. We found over 100 metabolites to be altered in plasma post exposure and after the corresponding decompression procedures. Among them, a group of lysophosphatidylcholines and lysophosphatidylethanolamines were increased, including lysoplasmalogen, a thrombosis promoter, together with changes in metabolic rate-associated molecules such as acylcarnitines and hemolysis-related compounds. Moreover, three metabolites that could be associated to bone degradation show different intensities between experimental groups. Ultimately, this nontargeted, short-term study opens the possibility of discovering markers of long-term effect of pressure that could be employed in routine health control of divers and could facilitate the development of safer decompression procedures.