We use electronic structure calculations to examine the impact of trace flue gas contaminants (nitrogen oxides, sulfur oxides, and their hydrates) on two promising coordinatively unsaturated metal−organic framework (MOF) sorbents. Such MOFs have been the subject of recent intense study since their unsaturated "open metal" sites yield dramatically enhanced uptake of CO 2 at low partial pressures, ideal for flue gas separation applications. However, the impact of these contaminants on gas adsorption and separation has not been seriously considered. Our computational results suggest that the open metal sites are subject to poisoning by these trace flue gas contaminants. Thus, despite the low (postscrubbing) concentrations of these contaminants, their binding enthalpy is sufficient to outcompete CO 2 for binding sites under equilibrium adsorption conditions and (by some estimates) even putative regeneration conditions. This work thus provides guidelines for identifying relevant contaminant species and illustrates the practical concerns in utilizing MOFs in realistic flue gas separation applications.