Here we present a comprehensive study of the thermodynamic parameters (enthalpy, entropy, and volume changes) associated with carbon monoxide photodissociation and rebinding to Fe(II) microperoxidase-11 (Fe(II)MP11) and Fe(ll) tetrakis(4-sulfonatophenyl)porphine complex (FeII4SP) with water and 2-methylimidazole as proximal ligands. CO photodissociation from FeII4SP complexes is accompanied by a positive volume change of approximately 17 mL mol(-1). A smaller volume change of approximately 12 mL mol(-1) was observed for CO dissociation from Fe(II)MP-11. We attribute the positive volume change to cleavage of the Fe-CO covalent bond and to solvent reorganization due to the low-spin to high-spin transition. CO binding is an exothermic reaction with an enthalpy change of -17 kcal mol(-1) for the CO-FeII4SP complexes and -13 kcal mol(-1) for the CO-Fe(II)MP11 complex. In all cases, the ligand recombination occurs as a single-exponential process indicating that CO dissociation is followed by direct CO rebinding to a high-spin five-coordinate complex without concomitant dissociation of the proximal base. In addition, observed negative activation entropies and volumes for ligand binding to (2-Melm)FeII4SP and MP-11, respectively, suggest that CO rebinding can be described by an associative mechanism with bond formation being the rate-limiting step.