SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection . To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid . We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion . The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states . In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction . Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection . These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction . Our findings suggest a role for anti-inflammatory treatment (s) in the management of neurologic complications of COVID-19 infection.