Abstract: OBJECTIVE To analyze the association of gene polymorphisms of apolipoprotein E（ApoE） and 5-hydroxytryptamine 2A（5-HT2A） receptor with mental disorders in children with viral meningitis. METHODS The clinical data were collected from 102 children with viral meningitis who were treated in Chongqing Liangjiang New Area First People's Hospital from Jan 2019 to Dec 2021, the children were divided into the severe group with 39 cases and the mild group with 63 cases according to the clinical symptom of mental disorders, meanwhile, 36 children who received physical examination were chosen as the control group. The frequencies of genotypes and alleles at loci of ApoE gene and 5-HT2A receptor gene were compared among the three groups, and the relationship between the gene polymorphisms of ApoE and 5-HT2A and the treatment outcomes of the viral meningitis children with mental disorders was observed. RESULTS The frequencies of TC/CC genotype and allele C at rs429358 locus of ApoE gene were higher in the severe group than in the mild group and the control group（P＜0.05）, which were higher in the mild group than in the control group（P＜0.05）.The odds ratio（OR） of severe viral encephalitis was 2.813 in the children with TC/CC genotype at rs429358 locus of ApoE gene. The frequencies of TT genotype and allele T at rs6313 locus of 5-HT2A receptor gene were higher in the severe group than in the mild group and the control group（P＜0.05）, which were higher in the mild group than in the control group（P＜0.05）. The OR of severe viral encephalitis was 2.375 in children with TT genotype at rs6313 locus of 5-HT2A receptor gene. In the severe group, the remission time of mental disorders, length of intensive care unit stay and total length of hospital stay of the children with TC/CC genotype at rs429358 locus of ApoE gene and TT genotype at rs6313 locus of 5-HT2A receptor gene were longer（P＜0.05）. CONCLUSION The polymorphisms at rs429358 locus of ApoE gene and rs6313 locus of 5-HT2A receptor gene are closely associated with the mental disorders and prognosis of the children with viral meningitis, which may provide guidance for clinical diagnosis and treatment.