An integrated circuit device includes a substrate having adjacent first and second regions, and a device isolation structure in the substrate between the first and second regions. The first and second regions of the substrate may respectively include transistors configured to be driven at different operational voltages, and the device isolation structure may electrically separates the transistors of the first region from the transistors of the second region. The device isolation structure includes outer portions immediately adjacent to the first and second regions and an inner portion therebetween. The outer portions of the device isolation structure comprise a material having an etching selectivity with respect to that of the inner portion. Related devices and fabrication methods are also discussed.