High-entropy alloys offer promising hydrogen storage properties and design versatility but suffer from compromised capacity and stability in practical industrial applications owing to surface poisoning caused by trace impurities or unexpected contact with air. Theoretical simulations provide a rapid and efficient platform for estimating anti-poisoning performance, particularly concerning alloys versus metal elements in various phases. This work explores the surface poisoning behavior of two typical high entropy materials: BCC-phase V₃₅Ti₃₀Cr₂₅Fe₁₀ and Laves-phase ZrTiVNiCrFe, along with pure metals V, Ti, Cr, and Fe as well as single AB₂ (A = Zr, Ti, B = V, Ni, Cr, and Fe) compounds, at various phase stages during hydrogen storage cycles using density functional theory (DFT) simulations. Results show that surfaces of V₃₅Ti₃₀Cr₂₅Fe₁₀ and ZrTiVNiCrFe with a hydrogen uptake of 100% can facilitate O₂ adsorption over dissociation, especially when O₂ adsorbs on Fe sites, and formation of hydroxyl. The O₂ poisoning behavior of high-entropy alloys was roughly estimated using the molar ratio weighted sum of constituent components, with the maximum deviation of 15.92% between predicted values and calculated values. This study sheds light on anti-poisoning mechanisms and aids in designing resilient high-entropy alloys.