Cytochrome P450s (CYP) are a family of iron heme-containing mono-oxygenases that can catalyze the hydroxylation of non-activated C-H bonds. This is one of the more difficult chemical reactions to achieve, involving the insertion of one atom from molecular oxygen which is activated by a reduced organic heme- iron. The nature of the catalytic mechanism has been a subject of controversy for nearly fifty years. Most of the computational studies have used the B3LYP density functional, but this functional routinely underestimates barrier heights and bond dissociation enthalpies (BDE). The M06-2X functional has been used lately as it provides better BDE’s, especially for peroxide O-O bonds. However, M06-2X can have difficulties for high spin states, particularly for transition metals. A recent study compared the performance of 250 density functionals in describing the spin states and binding energies for a number of porphyrin complexes. We have chosen representatives of the best functionals to examine key intermediates in possible reactions steps for cytochrome P450 oxidation reaction. Specifically, we have compared the B97XD, APFD, B3PW91, O3LYP, PBE1PBE and r2SCAN functionals with B3LYP and M06-2X. The best functionals appear to be B97XD, B3PW91 and PBE1PBE.