Introduction. Carbon monoxide (CO) poisoning causes hypoxia that results tissue injury, especially in the brain and heart. Delayed neurologic sequela is one of the most serious complications that may occur up to 40% of severe CO poisoning cases. Objective. The aim of the study was to determine an association between the serum tau protein and severe neurologic symptoms/signs upon presentation. Methods. Seventy-eight patients with CO poisoning were evaluated in this cross-sectional study. The patients were divided into two groups, Group 1: those with loss of consciousness (LOC)/syncope, seizure, coma, altered mental status (n = 19), and Group 2; without LOC (n = 59). Serum tau protein levels were studied on admission. Results. Mean age of the patients was 37.3 +/- 15.4 and 53.6% were male. Headache was the most common presenting symptom observed among 67 patients (86%). The median serum tau protein level was 76.54 pg/mL (35.56-152.65) within group 1, 64.04 pg/mL (23.85-193.64) in patients within group 2 (p = 0.039), respectively. The median serum tau protein levels were 79.80 pg/mL (35.56-193.64) in patients who received HBO therapy and 65.79 pg/mL (23.85-167.29) in patients who did not receive HBO therapy (p = 0.032). The value of area under the curve was 0.642 for detecting CO poisoning with severe neurological symptoms. Conclusion. Although tau protein levels were significantly higher in patients with severe neurological symptoms; the difference did not reach a clinical significance. Further studies are needed in order to reveal the validity of tau protein for detecting neurological injuries in patients with CO toxicity.