Abstract Background Dual-energy computed tomography has shown a great interest for musculoskeletal pathologies. Photon-counting spectral computed tomography (PCSCT) can acquire data in multiple energy bins with the potential to increase contrast, especially for soft tissues. Our objectives were to assess the value of PCSST to characterise cartilage and to extract quantitative measures of subchondral bone integrity. Methods Seven excised human knees (3 males and 4 females; 4 normal and 3 with osteoarthritis; age 80.6 ± 14 years, mean ± standard deviation) were scanned using a clinical PCSCT prototype scanner. Tomographic image reconstruction was performed after Compton/photoelectric decomposition. Virtual monoenergetic images were generated from 40 keV to 110 keV every 10 keV (cubic voxel size 250 × 250 × 250 μm 3 ). After selecting an optimal virtual monoenergetic image, we analysed the grey level histograms of different tissues and extracted quantitative measurements on bone cysts. Results The optimal monoenergetic images were obtained for 60 keV and 70 keV. Visual inspection revealed that these images provide sufficient spatial resolution and soft-tissue contrast to characterise surfaces, disruption, calcification of cartilage, bone osteophytes, and bone cysts. Analysis of attenuation versus energy revealed different energy fingerprint according to tissues. The volumes and numbers of bone cyst were quantified. Conclusions Virtual monoenergetic images may provide direct visualisation of both cartilage and bone details. Thus, unenhanced PCSCT appears to be a new modality for characterising the knee joint with the potential to increase the diagnostic capability of computed tomography for joint diseases and osteoarthritis.