Long COVID patients with severe sleep disturbance showed depleted levels of specialized pro-resolving mediators (SPMs) including 17-HDHA, resolvin D1, lipoxin B4, and protectin D1, while simultaneously exhibiting elevated prostaglandin E2 levels compared to recovered COVID patients. The 39-participant study found those with PROMIS sleep scores above 60 had significantly impaired inflammatory resolution pathways. This represents a crucial mechanistic discovery linking sleep quality to chronic inflammation in Long COVID. The finding illuminates why millions of Long COVID sufferers remain trapped in inflammatory cycles—their disrupted sleep prevents the body's natural resolution of inflammation through omega-3-derived mediators. This creates a vicious cycle where inflammation worsens sleep, which further impairs the biological machinery needed to resolve inflammation. The research suggests targeted interventions promoting SPM production could break this cycle. While the small sample size limits generalizability, the mechanistic clarity is compelling. For the estimated 65 million people worldwide with Long COVID, optimizing sleep quality may be as critical as any pharmaceutical intervention. This finding also has broader implications for other chronic inflammatory conditions where sleep disturbance is prevalent, suggesting SPM-targeted therapies could address multiple health challenges simultaneously.