Axial and radial specimens of non-degenerate and degenerate human anulus fibrosus (AF) were tested in confined compression to test the hypothesis that degeneration significantly affects the compressive properties of AF. Due to the highly oriented structure of AF, a secondary objective was to investigate anisotropic behaviors of AF in compression. Uniaxial swelling and stress–relaxation experiments were performed on site-matched samples of anulus from the anterior outer region of L2–3 intervertebral discs. The experimental stress–relaxation behavior was modeled using the finite deformation biphasic theory and a finite-difference approximation scheme. Significant effects of degeneration but not orientation were detected for the reference stress offset, σ_offset, and parameters describing the compressive stiffness (i.e. reference aggregate modulus, H_A0, and nonlinear stiffening coefficient, β). Average values were 0.13±0.06 and 0.05±0.05 MPa for σ_offset, 0.56±0.21 and 1.10±0.53 MPa for H_A0 and 2.13±1.48 and 0.44±0.61 for β for all normal and degenerate specimens, respectively. No significant effect of degeneration or orientation were detected for either of the parameters describing the strain-dependent permeability (i.e. reference permeability, k₀, and strain-dependent permeability coefficient, M with average values for all specimens of 0.20±0.10×10^-15 m⁴/N^–s and 1.18±1.30 for k₀ and M, respectively. The loss of σ_offset was compensated with an elastic stiffening and change in the shape of the equilibrium stress–strain curve with H_A0 for degenerate tissues almost twice that of normal tissues and β less than one sixth. The increase in reference elastic modulus with degeneration is likely related to an increase in tissue density resulting from the loss of water content. The significant effects of degeneration reported in this study suggested a shift in load carriage from fluid pressurization and swelling pressure to deformation of the solid matrix of the AF. The results also suggest that the highly organized and layered network of the anulus fibrosus, which gives rise to significant anisotropic effects in tension, does not play a major role in contributing to the magnitude of compressive stiffness or the mechanisms of fluid flow of the anulus in the confined compression configuration.