Objective To explore the association between multiple virus infections and sleep disorder based on the National Health and Nutrition Examination Surveys (NHANES) database. Methods The cross⁃sectional investigation data from 2009 to 2010 were selected from the NHANES database, and the research subjects were assigned to sleep disorder group or non⁃sleep disorder group according to the occurrence of sleep disorder. The baseline characteristics of research subjects in both groups were balanced by using the inverse probability of treatment weighting (IPTW). The balance of baseline characteristics of both groups before and after IPTW analysis was evaluated by employing the χ 2 test and standardized mean difference (SMD). The association between 7 virus infections and sleep disorder was analyzed by the application of unconditional Logistic regression (before IPTW analysis) and weighting Logistic regression (after IPTW analysis). A subgroup analysis was performed for the association between HAV infection and sleep disorder. Results A total of 2385 research subjects were enrolled, therein 146 research subjects were enrolled in the sleep disorder group, and 2239 research subjects were enrolled in the non⁃sleep disorder group. Before IPTW analysis, SMD of age, population, household income poverty impact ratio (PIR), and smoking in both groups was larger than 0.1, and the essential characteristics were imbalance. After IPTW analysis, there was no statistically significant difference in baseline characteristics between the two groups (SMD<0.1, P>0.05), and the essential characteristics were balance. The results of unconditional Logistic regression revealed that HAV infection, herpes simplex virus type 2 (HSV⁃2) infection exhibited correlations with sleep disorder (P<0.05). The results of weighting Logistic regression indicated that the occurrence risk of sleep disorder from HSV⁃2 infected person was approximately 1.93 times higher than that of uninfected person (P<0.05), whereas no correlation was found between HAV infection and sleep disorder (P>0.05). The subgroup analysis presented that the association between HAV infection and sleep disorder was significantly affected by age, educational level, and other confounding factors (Pinteraction< 0.05). Conclusion After balancing baseline characteristics by IPTW, there is a significant correlation between HSV⁃2 infection and sleep disorder. It is necessary to screen and intervene sleep disorder of HSV⁃2 infected person to improve its sleep quality.