This work is a first effort to prepare a low-density imprinted monolithic column for LC. The new molecularly imprinted polymer monolith was prepared with 30% (w/w) monomers in the pre-polymerization mixture while general high-density monoliths are prepared with 40% monomers. The resulting low-density (S)-naproxen-imprinted monolith produced better chiral resolution of rac-naproxen (R s = 1.55) and column efficiencies of imprinted molecules up to 2,860 plates m−1. Morphological characteristics of low density imprinted monolith was further studied by mercury intrusion porosimetry, scanning electron microscopy (SEM) and nitrogen sorption method. The experiments demonstrated that the strategy of low-density column may be one of a potential approach to the improvement of column efficiency of an imprinted stationary phase.