Many viruses can evolve different strategies to exploit the ubiquitin-proteasome pathway (UPP) for their own benefit. Some data have recently established connections between UPP and osteoarthritis (OA). The aim of this study was to determine the possible involvement of viral infections linked with the UPP in the physiopathology of OA. Samples of human cartilage were obtained from 12 patients with clinical and radiological features of OA and from 12 normal controls. DNA was extracted from cultured chondrocytes from these patients, and quantitative real-time PCR was performed to analyse the DNA/RNA prevalence and viral loads of HSV, EBV, HCMV, enterovirus, and HTLV-1. The prevalence of total viral DNA/RNA among patients with OA was 16.7% (mean viral load of 7.86 copies/mug DNA), EBV being responsible for the two positive samples, while the prevalence in controls was 0%. We did not detect any positive samples for HSV, CMV, enterovirus, and HTLV-1 among patients with OA and controls. This first approach to the study of the prevalence of viruses linked to the UPP in articular cartilage of end-stage OA patients provides evidences supporting the risk of EBV transmission or reactivation in a subset of patients with disorders requiring tissue regeneration.