Abstract Spectral photon-counting computed tomography (SPCCT) is a new technique with the capability to provide mono-energetic (monoE) images with high signal to noise ratio. We demonstrate the feasibility of SPCCT to characterize at the same time cartilage and subchondral bone cysts (SBCs) without contrast agent in osteoarthritis (OA). To achieve this goal, 10 human knee specimens (6 normal and 4 with OA) were imaged with a clinical prototype SPCCT. The monoE images at 60 keV with isotropic voxels of 250 × 250 × 250 µm 3 were compared with monoE synchrotron radiation CT (SR micro-CT) images at 55 keV with isotropic voxels of 45 × 45 × 45 µm 3 used as benchmark for cartilage segmentation. In the two OA knees with SBCs, the volume and densit...