Purpose: Decompression sickness (DCS) is a poorly understood and complex systemic disease caused by inadequate desaturation following a reduction of ambient pressure. A previous proteomic study of ours showed that DCS occurrence but not diving was associated with changes in the plasma proteome in rats, including a dramatic decrease of abundance of the tetrameric form of Transthyretin (TTR). The present study aims to assess the impact on the human blood proteome of a dive inducing significant decompression stress but without inducing DCS symptoms. Experimental design: Twelve healthy male divers were subjected to a single dive at a depth of 18 m of sea water (msw) with a 47-min bottom time followed by a direct ascent to the surface at a rate of 9 msw/min. Venous blood was collected before the dive as well as 30 min and 2 h following the dive. The plasma proteomes from four individuals were then analyzed by using a two-dimensional electrophoresis-based proteomic strategy. Results: No protein spot showed a significantly changed abundance (fdr<0.1) between the tested times. Conclusion: These results strengthen the hypothesis according to which significant changes of the plasma proteome measurable with two-dimensional electrophoresis may only occur along with DCS symptoms.