Cartilage exhibits remarkable low-friction and low-wear properties, which enable the tissue to withstand decades of repetitive loading cycles in vivo. Though osteoarthritis (OA) pathogenesis is highly variable across patients and multifactorial, inferior cartilage lubrication is a hallmark of OA. Despite the critical role of lubrication to joint health, our understanding of lubrication in disease is limited. Specifically, it is unclear how both of the critical synovial fluid lubricants, lubricin and hyaluronic acid (HA), are affected across different forms of OA. Furthermore, it is unclear how alterations in composition ultimately affect the lubricating properties of synovial fluid. Therefore, the overarching goal of this dissertation was to characterize synovial fluid lubrication in different forms and stages of OA. A holistic approach was applied whereby synovial fluid was examined for both lubricin and HA content as well as its mechanical properties including multi-modal friction coefficients, viscosities, and effective viscosities. This work contributes to the field’s knowledge of lubrication in disease and advances several important and novel concepts;​ notably, (1) the Stribeck framework was applied successfully for the first time to synovial fluid, (2) effective viscosities of synovial fluid were calculated and applied to compare lubricating properties, and (3) finally, the lubricating effect of HA viscosupplementation, a common OA therapeutic, was found to depend on synovial fluid composition.