Chemical-looping combustion (CLC) is one of the ways to achieve carbon capture. As an oxygen carrier (OC), CaSO4 is a potential candidate due to high oxygen capacity and low price. However, it is limited in terms of low reactivity. Although the reduction reaction process mechanism of CaSO4 OC has been calculated, the heterogeneous adsorption was not considered. To further investigate the mechanism of its low reactivity, the heterogeneous adsorption of CO on the CaSO4 surface and its reduced surfaces was calculated by a first-principles study, and the wave functions of the stable configurations were analyzed. The results show that the adsorption of CO on these surfaces is physical adsorption and the weak interaction is the main contribution. Moreover, the adsorption energies of the chi(OL) = 100-25% stage are -32.82, -32.13, -40.45, -44.25, and -6.80 kJ/mol. According to energy decomposition, the electrostatic interaction is the principal interaction for the attraction at the chi(OL) = 100-50% stage, and the electrostatic interaction and London dispersion interaction both contribute to the attraction at the chi(OL) = 25% stage. However, electrons transferring between CO and the surface are lower than 0.1e. Furthermore, the atoms-in-molecules (AIM) and independent gradient model (IGM) analyses indicate that the interaction of CO and the chi(OL) = 25% surface is very weak. At the chi(OL) = 100-50% stage, the interaction of CO and the surface is the pure closed-shell interaction, and C-Ca interaction contributes the most to the weak interaction. To improve the reactivity of a CaSO4 oxygen carrier, further research works could follow the direction of increasing the electron transferability to improve the adsorption ability, such as exposing more active surfaces.