Abstract: Objective To analyze the levels of neuron-specific enolase(NSE), myelin basic protein(MBP), S-100 protein(S-100)in cerebrospinal fluid and serum of children with viral encephalitis. Methods A total of 205 viral encephalitis cases were selected as observation group, which were subdivided into mild group(n=112)and severe group(n=93)according to the severity of the disease. Another 200 healthy children in the same period were selected as control group. The levels of NSE, MBP and S-100 in the cerebrospinal fluid and serum of children in two groups were detected and compared. Results The levels of NSE, MBP and S-100 in cerebrospinal fluid and serum of the observation group at 24 h after admission were significantly higher than those of the control group, while were significantly lower in the mild group than those in the severe group(P<0.05). The sensitivity and accuracy of combined detection of NSE, MBP and S-100 were 91.22% and 89.14% respectively, which were significantly higher than those detected by single detection(P<0.05). There was no significant difference in the specificity between combined detection and single detection(P>0.05). Conclusion The levels of NSE, MBP and S-100 in cerebrospinal fluid and serum are closely related to the disease condition of children with viral encephalitis, and their combined detection is of significant diagnostic value.