Updated project metadata. In order to better understand physiological mechanisms and neurological symptoms involved in the development of decompression sickness we determined effects in rats on the brain proteome of fast decompression (1 bar/20 s) compared to controls (1 bar/10 min) after heliox saturation diving. The orbitrap LC-MS/MS data files presented here resulted in 1062 proteins quantified using label-free proteomics. Based on the 128 significantly regulated proteins in the orbitrap dataset and 56 in an iontrap dataset (967 quantified proteins), the networks “synaptic vesicle fusion and recycling in nerve terminals” and “translation initiation” were significantly enriched in a system biological database analysis (Metacore). Ribosomal proteins (RLA2, RS10) and the proteins hippocalcin-like protein 4 and proteasome subunit beta type-7 were significantly upregulated in both datasets. The heat shock protein 105 kDa, Rho-associated protein kinase 2 and Dynamin-1 were significantly downregulated in both datasets.