Purpose: Epidemics of emerging diseases severely affect economies, consumption, and investment. Thus, this exploratory study investigated the importance level of business operations in epidemics of emerging diseases, compared the importance placed on such operations among small, medium, and large enterprises, and developed a structural equation model of such operations. Methodology: Using multistage sampling, data were collected by interviewing 500 Thai entrepreneurs operating small, medium, and large enterprises registered as juristic persons. The mean and standard deviation were used to ascertain the level of importance of business operations in epidemics. The importance level of such business operations among small, medium, and large enterprises was compared using F-values obtained from Analysis of Variance. The structural model was tested using structural equation modeling. Findings: Business operations in epidemics were divided into five areas: financial capability, operation transformation, personnel development, innovation deployment, and material sourcing. Comparing the importance level of business operations among small, medium, and large enterprises showed that two out of five latent variables, personnel development and material sourcing, differed at the 0.05 significance level. Furthermore, operation transformation had the most direct impact on innovation deployment. Originality: This study shows that the digital economy allows micro and small enterprises to reach more consumers and reduces the investment required to start a business, but this does not guarantee that all small and medium enterprises are ready for digital transformation.