Many theoretical investigations accordingly employ smaller clusters or hybrids between quantum mechanics and molecular mechanics (QM/MM). In the latter methods, the main part of the enzyme is included within the MM region. Unfortunately, results from both QM cluster models and QM/MM methods can depend significantly on the computational setup. A particular issue is that results tend to converge slowly with increasing QM system size. For LPMOs, the theoretical studies have obtained reaction energies and barriers for several crucial steps in the reaction mechanism that differ quite significantly. While LPMOs display large differences among themselves, theoretical studies have even obtained different results employing a setup with outset in the same crystal structure: the LPMO from LsAA9 has been employed in several theoretical studies, since it is among the few LPMOs for which enzyme-substrate complexes have been crystallised. We have previously found from DFT-based QM/MM calculations that both O 2 -and H 2 O 2 -driven pathways were feasible, although the latter was favorable. Other theoretical work exclusively investigated the H 2 O 2 -driven mechanism, 36 but obtained rather large differences in structures and energetics of key intermediates compared to ref. 37. The theoretical investigations relied on different choices of QM region, and neither consistently employed the second-sphere residues known to be important from mutation studies. Curiously, later experimental results have indicated that the LsAA9 is among the LPMOs that exclusively employ H 2 O 2 as co-substrate, severely questioning the theoretical results for the O 2 -driven pathway. In this paper, we investigate both the O 2 -and H 2 O 2 -driven pathways, based on the LsAA9 substrate-complex crystal structure. We employ extended QM regions and, therefore, consistently include all residues known to be important. Moreover, we employ several different DFT functionals to ensure that previous discrepancies between different theoretical investigations are not a result of different choices of DFT functionals. With this setup, we obtain a mechanism that better aligns with recent experimental results and we can correct previous theoretical estimates for reaction energies and barriers.