Cell survival of thick engineered scaffolds is often compromised due to limited oxygen diffusion. Therefore, the design of oxygen-delivering nanofibrous polyurethane (PU)-calcium peroxide (CPO) scaffolds was investigated in this study. The average size of CPO nanoparticles was [Formula: see text][Formula: see text]nm. The average diameter of PU fibers was [Formula: see text]m, which was increased to [Formula: see text], [Formula: see text], and [Formula: see text]m upon incorporation of 0.1[Formula: see text]wt.%, 0.5[Formula: see text]wt.% and 1[Formula: see text]wt.% CPO, respectively. The CPO-containing scaffolds could produce oxygen for at least 13 days. Samples containing 0.5% CPO showed the highest oxygen release without a significant change in pH. For this sample, the addition of ascorbic acid as an antioxidant to counteract the possible formation of ROS, reduced the fiber diameter to [Formula: see text]m and increased the oxygen release. Adding 0.5% CPO improved the cell viability on the fifth day. In addition, the PU-CPO composite scaffold showed strong antibacterial activity. Overall, designed scaffolds could be useful in different tissue engineering applications to overcome the limited oxygen availability early after implantation.