Particulate methane monooxygenase (pMMO) is the most efficient of the two groups of enzymes that can hydroxylate methane. The enzyme is membrane bound and therefore hard to study experimentally. For that reason, there is still no consensus regarding the location and nature of the active site. We have used combined quantum mechanical and molecular mechanical (QM/MM) methods to study the reactivity of the CuB site with a histidine brace and two additional histidine ligands. We compare it with the similar active site of lytic polysaccharide monooxygenases. We show that the CuB site can form a reactive [CuO]+ state by the addition of three electrons and two protons, starting from a resting Cu(II) state, with a maximum barrier of 72 kJ mol-1. The [CuO]+ state can abstract a proton from methane, forming a Cu-bound OH- group, which may then recombine with the CH3 group, forming the methanol product. The two steps have barriers of 59 and 52 kJ mol-1, respectively. However, in many of the steps, formation and dissociation of H2O2 or HO2- compete with the formation of the [CuO]+ state and the former steps are typically more favourable. Thus, our calculations indicate that the CuB site is not employed for methane oxidation, but may rather be used for the formation of hydrogen peroxide. This conclusion concurs with recent experimental investigations that excludes the CuB site as the site for methane oxidation.