The present invention relates to spacer fluids used in subterranean operations and, more particularly, to spacer fluids that comprise water-soluble relative permeability modifiers and methods of using the spacer fluids in subterranean operations. In one embodiment, the present invention provides a method of displacing a first fluid from a well bore that comprises introducing the first fluid into the well bore; and displacing the first fluid with a spacer fluid, the spacer fluid comprising water, and a water-soluble relative permeability modifier comprising a hydrophobically modified polymer or a hydrophilically modified polymer. In another embodiment, the present invention provides a spacer fluid that comprises water, and a water-soluble relative permeability modifier comprising a hydrophobically modified polymer or a hydrophilically modified polymer.