Octahedral molecular sieve (OMS) materials classified by their different tunnel sizes are defined by edge-sharing MnO6 octahedra. Four different OMS materials (OMS-1, OMS-2, OMS-5, and OMS-6) are benchmarked for ethane (C2H6) and cyclohexane (C6H12) oxidative dehydrogenation (ODH) and compared with commercial MnO2, M1 phase MoVTeNb oxide, and vanadium oxide (V2O5). The accessibility of the quadrilateral tunnels of the OMS materials to C2H6 and C6H12 were further evaluated using density functional theory (DFT). C2H6 and C6H12 ODH rates for the four OMS materials were higher than those measured for commercial MnO2, MoVTeNbO, and V2O5. The C2H6/C6H12 rate ratios on the four OMS oxides are larger than V2O5. Rate relations for selective accessibility for C2H6 in small pores, accessibility to both molecules in large pores, and the presence of tunnel defects are discussed. Product selectivities show slightly higher ethylene selectivity in smaller pores suggesting possible connections between pore confinement and selectivity. Porous octahedral molecular sieves displaying different tunnel structures are prepared to study Oxidative dehydrogenation (ODH) reaction using ethane and cyclohexane as substrates. The assessment of the micropore and mesopore pore volumes and compared to the ethane to cyclohexane rate ratios. A relationship in ODH rates and pore sizes and pore volumes was observed, with larger tunnel sizes not being discriminatory to either substrate compared to smaller tunnels that are highly active for ethane and not cyclohexane. Graphic created using Biorender.com Display omitted •Oxidative dehydrogenation using Octahedral Molecular Sieves (OMS).•Determination of microporous and mesoporous pore volumes and ratios.•A possible connection between pore confinement and selectivity from ethylene ODH.•C2H6 and C6H12 ODH rates for OMS materials were higher than measured for standards.