Background and Objective: Knee surgery attempts to restore the native biomechanics of the knee, improve stability, and decrease the progression of osteoarthritis (OA). However, despite improvements in surgical techniques, tissue degradation and OA are common after knee surgery, occurring in higher rates in surgical knees compared to non-surgical knees. The aim of this study is to analyze previous literature to determine which synovial fluid biomarkers contribute to knee tissue degradation and decrease patient outcomes in the post-surgical setting of the knee. Methods: A narrative review of relevant literature was performed in July 2023. Studies reporting on synovial biomarkers associated with the post-surgical knee were included. Key Content and Findings: The literature reported that proinflammatory synovial biomarkers cause cartilage degradation and turnover which eventually leads to OA. The associated biomarkers are typically present prior to physical symptoms so understanding which one’s correlate to OA is important for potential therapeutic treatments in the future. Studying the preoperative, early postoperative, and late postoperative synovial biomarkers will allow physicians to develop an improved understanding of how these biomarkers progress and correlate to knee tissue degradation and OA. This understanding could lead to further developments into potential treatment options. Research into inhibiting or reversing these inflammatory biomarkers to slow the progression of knee tissue degradation has already begun and has reported some promising results but is currently limited in scope. Conclusions: Synovial fluid biomarkers in the post-surgical knee setting may contribute to decreased patient outcomes and the progression of knee tissue degradation. There is no current consensus on which of these biomarkers are the most detrimental or associated with decreased patient outcomes. With an improved understanding of the individual biomarkers, potential personalized therapeutic treatment could be used by physicians in the future to improve patient outcomes after surgery.