In previous studies, after injury, burn patients experienced an increase in neuro-inflammation, edema, and neuronal cell death. As demonstrated in other brain injury models, fluid-based biomarkers such as phosphorylated neurofilament-H (pNFL-H) have been shown to correlate with injury severity. In this study the authors hypothesized that burn-injured patients have an increase in pNFL-H in the blood during the acute and chronic time-points after injury. In this prospective clinical study, blood (8 cc) was collected from burn patients (n = 36; TBSA 10-60%) at Parkland hospital, Dallas, Texas, on days 1, 7, and 14 after injury. The serum levels of pNFL-H were measured using the enzyme-linked immunoassay. Compared to noninjured controls, the burn patients exhibited a significant increase in the serum levels of pNFL-H on days 7 (P < .0001) and 14 (P < .0001) after burn injury. No significant increase was observed on day 1 (P < .07) after injury. A positive correlation between TBSA and pNFL-H levels was observed for day 14 (r = .55; P < .03). Additionally, using the receiver operating characteristic analysis, the authors determined the area under the curve was 98% for both day 7 and 14. In conclusion, this study describes the serum profile of pNFL-H in patients suffering from severe burns during the acute (day 1) and chronic (days 7 and 14) time-points. These results suggest that detection of pNFL-H may be useful in determining which individuals suffer from nerve cell degeneration after burn.