We consider carbon monoxide (CO) confined in the hydrogenbonded building blocks of sI and sII clathrate hydrates, viz., (5 12 , 5 12 6 2 , 5 12 6 4 ) cages, within the density functional theory-based calculations. We study their response to the applied electric fields in terms of changes in the geometrical parameters, dipole moment, HOMO−LUMO gap, and vibrational frequency shift. We examine the stability of CO clathrate hydrate building block cages and identify a possible indication of the field-induced release of CO.