Exposure to hyperbaric environments and subsequent decompression has been associated with many physiological alterations, which may culminate in decompression sickness, a disease that might manifest itself through a variety of symptoms, ranging from joint and/or musculoskeletal pain, to cardiovascular and neurological impairment and, ultimately, death.Historically, decompression studies have adopted a binary approach, separating post decompression events between symptomatic and asymptomatic. There is, however, a huge spectrum of possible physiological alterations between these two extremes to which probabilities of decompression sickness occurrence are likely to be associated, based on individual responses. The purpose of this study is to analyze the correlation between decompression-related physiological stress markers, given by inflammatory processes and immune system activation and changes in Heart Rate Variability, evaluating whether Heart Rate Variability can be used to estimate the physiological stress caused by a given decompression profile. A total of 28 volunteers participated in two different experimental protocols, divided in two different compression-decompression profiles, both with same maximum pressure and duration, but with different decompression schedules.Electrocardiograms and endothelial function evaluations, measured through Pulse Wave Amplitude were performed; blood samples were obtained for the quantification of red cells, hemoglobin, hematocrit, neutrophils, lymphocytes, platelets, aspartate transaminase (AST), alanine aminotransferase (ALT), and for immunophenotyping and microparticles (MP) research through Flow Cytometry, before and after each experimental protocol from each volunteer. Also, myeloperoxidase (MPO) expression and microparticles (MPs) deriving from platelets, neutrophils and endothelial cells were quantified. The results obtained demonstrated a clear distinction between the outcomes of the different decompression profiles in most indicators used to quantify decompression-related physiological stress.There is an association between HRV reduction and MPO, MPs production, platelet count and neutrophils activation markers. The decompression profile with decompression stops at higher ambient pressures was associated with higher counts of MPs and neutrophil 4 activation, quantified by MPO expression in addition to reduced HRV and endothelial function.