Background and Objective: Health Literacy (HL), defined as the ability to access/obtain, understand, appraise/judge/evaluate, apply/use health-related information, has a direct impact on the capacity of managing three main domains of health-relevant information: Health Care (HC), Disease Prevention (DP), and Health Promotion (HP), which are fundamental for improving individual and population health. Methods: In 2021, a national survey of a representative sample of the Italian population aged 18+ years (N=3,500) was conducted in the framework of the WHO M-POHL (Measuring Population and Organizational Health Literacy) network. The validated HL questionnaire at 12 items (HLS-Q12) included general HL, sociodemographic characteristics, risk factors, lifestyles sections. For each of the 3 HL domains, 4 items were analysed. For each HL-item, a 4-point Likert scale was applied: very easy, easy, difficult, very difficult. For the 3 HL domains (healthcare, disease prevention, health promotion), the percentage of very easy+easy answers was used as a score and classified in 5 groups (0%, 25%, 50%, 75%, 100%). Results: For all the 3 HL domains, the majority of participants were in the 75% and 100% groups (63.1% for HC, 56.8% for DP, 70.7% for HP). They were mostly in the 18-29 age group (72.3% for HC, 59.9% for DP, 72.7% for HP), women for HP only (72.5%), with a high educational level (66.6% for HC, 59.0% for DP, 72.4% for HP), living in north western regions (65.1% for HC and 58.4% for DP) and central Italy (74.2% for HP). Conclusions: The results on HL domains of the general HL highlighted the need to improve HL especially in adult and elderly population, in those with a lower level of education, and in the Southern and Central areas of the country. Better HL level could improve the general population’s ability to manage health information regarding care, prevention, and promotion of health.