Cooperative interactions are a central feature of protein structure, influencing a wide range of important phenomena including protein folding, allostery and protein-protein interactions. The universal assumption spanning more than fifty years of work, yet still untested, is that cooperative interactions are not present in the denatured state ensemble (DSE) of proteins. Here we demonstrate that energetically significant specific cooperative coupling occurs in the denatured state of globular proteins, even for residues, which are distant in sequence and spatially well separated from each other in the native structure.