<p>The knee joint facilitates movement essential for daily activities. Its intricate anatomy makes it particularly prone to injury, specifically to the anterior cruciate ligament (ACL). ACL injury is a leading cause of post-traumatic osteoarthritis (PTOA), a degenerative joint disease that affects millions and results in pain, decreased mobility, and reduced quality of life. The cascade of initial inflammatory activity triggered by ACL injury plays a critical role in the pathogenesis of PTOA, as elevated levels of pro-inflammatory cytokines and catabolic enzymes lead to ongoing joint damage and dysfunction.</p><p>Omega-3 fatty acids, an essential component of our diet, have been demonstrated to exert protective effects on joint tissues by modulating inflammatory pathways and promoting tissue repair. Specifically, these fatty acids diminish the production of inflammatory cytokines and enhance the resolution of inflammation, thereby potentially reducing the progression of PTOA. Given the lack of effective preventative therapies for PTOA, there is a pressing need for strategies that target early inflammatory processes to slow disease progression. This review provides a comprehensive analysis of the mechanistic and biochemical pathways through which these fatty acids influence knee joint health, with a focus on their impact in PTOA. By investigating the roles of omega-3 fatty acids and their metabolites, eicosanoids and specialized pro-resolving mediators, we highlight the potential for a nutrition based therapeutic application in managing PTOA.</p>