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The influence of water on the mechanical properties of rocks has been observed by many researchers in rock engineering and laboratory tests, especially for sedimentary rocks. In order to investigate the effect of water saturation on the mechanical properties of low-permeability rocks, uniaxial compression tests were conducted on siltstone with different water contents. The effects of water on the strength, elastic moduli, crack initiation and damage thresholds were observed for different water saturation levels. It was found that 10% water saturation level caused more than half of the reductions in mechanical properties. A new approach is proposed to analyze the stress-strain relations at different stages of compression by dividing the axial and lateral stress-strain curves into five equal stress zones, where stress zones 1–5 refer to 0%–20%, 20%–40%, 40%–60%, 60%–80% and 80%–100% of the peak stress, respectively. Stress zone 2 represents the elastic range better than stress zone 3 which is at half of the peak stress. The normalized crack initiation and crack damage stress thresholds obtained from the stress-strain curves and acoustic emission activities averaged 31.5% and 83% of the peak strength respectively. Pore pressure is inferred to take part in the deformation of low-permeability siltstone samples, especially at full saturation levels. A change of failure pattern from multi-fracturing to single shear failure with the increase of water saturation level was also observed.