Calcium peroxide (CaO2), one of versatile and harmless inorganic peroxy compounds, has been recently used as a highly effective oxidant to degrade pollutants in sludge and a method to achieve sludge resource utilization. However, its impact on hydrogen production has never been studied before. This investigation therefore aims to fill this knowledge gap. Results indicated that with CaO2 increased from 0.05 to 0.25 g/g VSS (volatile suspended solids), the maximum hydrogen yield increased from 0.77 to 10.55 mL/g VSS. The mechanism studies revealed that CaO2 accelerated the breakage and death of sludge cells. Excitation emission matrix (EEM) analyses further indicated that CaO2 increased the biodegradability of the released substances, which could provide more biodegradable organics for the following reactions. Although CaO2 caused inhibitions to some extents to all the tested microbes, its inhibition to hydrogen consumers was much severer than that to hydrolytic microbes and hydrogen producers. The enzyme analyses also demonstrated that the suppression of calcium peroxide to the activities of enzymes related to hydrogen consumption process was much severer than that to the activities of the activities of enzymes related to hydrogen production process. Further investigations exhibited that alkali, center dot O-2(-) and center dot OH radicals, were the major intermediate products of CaO2 decomposition. All of them were verified to contribute the increased hydrogen production, and their contributions were in the order of alkali > center dot O-2(-) > center dot OH. This is the first work demonstrating that CaO2 can enhance hydrogen production from WAS. The findings reported in our paper not only expand the application field of CaO2 but also deepen the understanding of the CaO2-involved sludge fermentation process.