COVID-19 infection among pregnant women results in more severe symptoms and higher mortality rates. No comprehensive health literacy for protection against COVID-19 among pregnant women has been available for general use in Thailand. This cross-sectional study aimed to develop and examine an instrument for measuring health literacy of prevention COVID-19 infection among pregnant women (HLS-P). A total of 321 pregnant women aged older than 20 years were participated in this study, Selected through multistage cluster sampling, between September 2021 and January 2022. Data were collected using structured questions that included sociodemographic characteristics and the health literacy scale for protecting against COVID-19 (HLS-P) developed by the researchers. The content and construct validity of the health literacy scale were examined. Exploratory factor analysis performed with principal component analysis and Varimax rotation. Confirmatory factor analysis was conducted using IBM SPSS AMOS 26. The model fitting was evaluated using several indices namely root mean square error of approximation, normed fit index, comparative fit index, and goodness-of-fit index. The reliability of the scale was evaluated using Cronbach's alpha and item total correlation. As a results of exploratory factor analysis of the scale, 31 items were loaded which indicated a 6-factors for the scale that collectively explained 62.59% of total variance. Confirmatory factor analysis also indicated a good fit to the six latent structures with root mean square error of approximation 0.03, normed fit index 0.94, comparative fit index 0.97, and goodness-of-fit index 0.91. Internal consistency reliability was satisfactory with Cronbach's alpha coefficient of 0.94 and the item-total correlation between 0.34 and 0.86. The overall scale was sufficiently reliable. As a result, the HLS-P is a reliable and relevant measure for assessing health literacy in pregnant women. Thus, this scale is profoundly used as an evaluation tool for measuring health literacy among pregnant women, providing critical information for healthcare professionals and policymakers about the health literacy needs and capacity of service receivers.