The effect of water, methanol, and hexane vapors on gas permeability was studied in a hybrid membrane containing 5 wt% copolyimide brushes with poly(methyl methacrylate) side chains (PI-g-PMMA) in a poly(phenylene oxide) (PPO) matrix, and in a pristine PPO membrane. These membranes in the form of dense nonporous films were further examined by atomic force microscopy (AFM) and scanning electron microscopy (SEM), as well as by measuring their mechanical and gas transport properties. A gas separation study of the membranes in a dry state and the membranes saturated with water, methanol, and hexane vapors was performed to estimate the effect of each vapor on the H 2, CO 2, N 2 permeability and selectivity in the separation of H 2/N 2 and CO 2/N 2 pairs. In general, saturation with water, methanol, and hexane vapors caused a decrease in the gas permeability of both membranes. The hybrid membrane containing copolyimide brushes demonstrated enhanced selectivity in the separation of H 2/N 2 and CO 2/N 2 pairs. It was found that a special effect of the vapors used for membrane saturation is associated with their molar volume. The solubility and diffusion coefficients of N 2 and CO 2 were obtained by Grand Canonical Monte Carlo (GCMC) and molecular dynamics (MD) simulations.