Porous ultra-high molecular weight polyethylene (UHMWPE) is a high performance bioinert polymer used in cranio-facial reconstructive surgery in procedures where relatively low mechanical stresses arise. As an alternative to much stiffer and costly polyether-ether-ketone (PEEK) polymer, UHMWPE finds further wide application in hierarchically structured hybrids for advanced implants mimicking cartilage, cortical and trabecular bone tissues within a single component. The mechanical behaviour of open-cell UHMWPE sponges obtained through sacrificial desalination of hot compression-moulded UHMWPE-NaCl powder mixtures shows a complex dependence on the fabrication parameters and microstructural features. In particular, similarly to other porous media it displays significant inhomogeneity of strain that readily localises within deformation bands that govern the overall response. In this article, we report advances in the development of accurate experimental techniques for operando studies of the structure-performance relationship applied to the porous UHMWPE medium with pore sizes of about 250 µm that are most well-suited for live cell proliferation and fast vascularization of implants. Samples of UHMWPE sponges were subjected to in situ compression using a micromechanical testing device within Scanning Electron Microscope (SEM) chamber, allowing the acquisition of high-resolution image sequences for Digital Image Correlation (DIC) analysis. Special masking and image processing algorithms were developed and applied to reveal the evolution of pore size and aspect ratio. Key structural evolution and deformation localisation phenomena were identified at both macro- and micro-structural levels in the elastic and plastic regimes. The motion of pore walls was quantitatively described, and the presence and influence of strain localisation zones were revealed and analysed using DIC technique.