The mechanical properties and hydraulic permeabilities of biomaterial scaffolds play a crucial role in their efficacy as tissue engineering platforms, separation processors, and drug delivery vehicles. In this study, electrospun cellulose acetate fiber meshes of random orientations were created using four different concentrations, 10.0, 12.5, 15.0, and 17.5 wt % in acetone or ethyl acetate. The tensile mechanical properties and the hydraulic permeabilities of these meshes were measured, and a multiscale model was employed to predict their mechanical behavior. Experimentally, the elastic modulus ranged from 3.5 to 12.4 MPa depending on the polymer concentration and the solvent. Model predictions agreed well with the experimental measurements when a fitted single‐fiber modulus of 123.3 MPa was used. The model also predicted that changes in fiber alignment may result in a 3.6‐fold increase in the elastic modulus for moderately aligned meshes and a 8.5‐fold increase for highly align meshes. Hydraulic permeabilities ranged from 1.4 x 10−12 to 8.9 x 10−12 m2 depending on polymer concentration but not the choice of solvent. In conclusion, polymer concentration, fiber alignment, and solvent have significant impact on the mechanical and fluid transport properties of electrospun cellulose acetate fiber meshes. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.