Objective: To evaluate the usefulness of cerebrospinal fluid (CSF) and plasma neurofilament light (Nf-L) as a biomarker for HTLV-1-associated myelopathy (HAM). Methods: Nf-L, CXCL10 and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by SIMOA. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein and HTLV-1 proviral load. Results: Nf-L was detected in all CSF samples (Median (range) = 575pg/ml (791.8-2,349)) and positively correlated with markers of inflammation (CXCL10 (r= 0.733), neopterin (r= 0.499), cell count (r= 0.403) and protein levels (r= 0.693) in CSF; p<0.0015). There was an inverse correlation between Nf-L and duration of disease (r = -0.584, p<0.0001). Wheelchair dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10 and protein in CSF. Conclusions: Nf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuro-inflammation.