France participated for the first time in a survey on adult health literacy. Health literacy (HL) refers to the motivation and skills an individual needs to identify, understand, evaluate, and use health information to maintain and improve their health. It is considered a major determinant of population health. The Health Literacy Survey 2019–2021 (HLS19) is the result of an international collaboration led by the Action Network on Measuring Population and Organizational Health Literacy (M-POHL). This M-POHL network was established under the auspices of the WHO/Europe European Health Information Initiative (EHII) in February 2018. It builds on the first European Health Literacy Survey (HLS-EU 2009–2012). France participated in this collaboration alongside 15 other countries between 2019 and 2021. The main objectives of this survey were: 1) To validate the French adaptation of the health literacy measurement instruments developed prior to this survey; 2) To estimate the level of health literacy and the main difficulties among the general adult population residing in metropolitan France; 3) To study the sociodemographic determinants of health literacy; 4) To explore the associations between health literacy and other variables assessing health status and behaviors such as physical activity. An online survey was conducted in two waves (May 2020 and January 2021) among 2,003 adults residing in metropolitan France who are members of the Ipsos ISay panel. Respondents were selected using a quota sampling method that reflected the structure of the French population by age, gender, region, and area of residence. The questionnaire included: the mandatory questionnaire for participating in the international HLS19 survey: the general HLS-Q12 health literacy questionnaire and sociodemographic, behavioral, and health characteristics; optional modules on specific health literacy topics regarding navigating the healthcare system (LS-NAV), communication (LS-COM), and digital health literacy (LS-DIGI); a few items related to the research topics of the researchers involved in the COVID-19 pandemic. The analysis used to validate the scales shows that the various questionnaires assessing general health literacy (HLS-Q12) and specific health literacies (HL-NAV, HL-COM, HL-DIGI) possess acceptable psychometric properties, but the four calculated scores exhibit a ceiling effect of varying degrees in the survey. The results highlight a relatively high average general LS score (77.5/100). When classifying literacy levels into four categories—excellent, sufficient, problematic, or inadequate—these results must, however, be qualified, as 14.3% of respondents have an “inadequate” literacy level and 29.8% a “problematic” level. An inadequate literacy level is associated with a perceived unfavorable social status, financial difficulties, and chronic health problems. The average scores and levels on specific LS scales show greater variation. Indeed, the proportion of respondents with an inadequate level is 49.2% for Navigation LS, 18.5% for Communication LS (or Interactive LS), and 53.9% for Digital LS. These three specific scores are significantly (p