Background: Epilepsy is a complex neurological disorder that can significantly impact a person's life. Understanding the knowledge, Self-Management (SM) practices, and Health-Related Quality of Life (HR-QoL) of individuals with epilepsy is crucial for improving their care. However, limited research papers explored knowledge, SM skills and HR-QoL among Omani adults with epilepsy in Oman. Purpose: This study aimed to measure the level of patient knowledge, SM practices, and Health-Related Quality of Life (HR-QoL) among Omani adults with epilepsy Furthermore, the study aimed to investigate the potential correlations between these variables to understand better their interrelatedness and impact on the overall well-being of individuals with epilepsy. Methods A cross-sectional descriptive corelation design measuring knowledge, SM and HR-QoL among Omanı adults with epilepsy utilized standardized instruments (EKS) for knowledge (ESMS-38) for SM practices and QOLIE-31 for HR-QOL A convenience sample of 200 PWEs was recruited from three tertiary hospitals in Muscat Descriptive statistics (te, M. SD. frequency, and percentile) and inferential statistics (Pearson correlation coefficient, independent samples t-tests and One way ANOVA) utilized to analyse the data Results: The participants consisted of 200 adult Patients with Epilepsy (PWEs). Males constituted around half (52.5%) of the study sample Age (M-33.29, SD= ±10.75). The minimum and maximum age was 18 and 75 years, respectively The findings showed that the overall level of knowledge was poor, with a mean total score of 7.81 out of 19. Although the participants had acceptable SM skills (Af-131.60, SD 15.70) out of 190, the level of HR-QoL was on the lower side (M-56.55, SD-15.73) out of 100. However, among the five SM domains the Lifestyle and Information Management domains had the lowest score (M-18.56) and (M-16.85) respectively. The analysis revealed a non- significant correlation between patients' knowledge about epilepsy and their SM skills (p -0.710). However, a positive correlation was observed between knowledge and HR-Qol. (0.261, p=0.001), suggesting that patients with higher knowledge levels about epilepsy might experience a better HR-QoL and vice versa. Additionally, the relationship between SM practices and HR-QoL. was found to be non-statistically significant (p 0.104). The independent samples t-test and One-way ANOVA identified a significant association between SM practices and the use of an Antiseizure Medication (ASMs) lacosamide (p-value 0.01) Moreover, there was a significant association between HR- Qol and gender, males show higher QoL (Af-59.26) compared to females (M-53.55), employees have a better QoL. (M-59.57) compared to the unemployed (AM-53.58), patients with other comorbidities report a lower HR-QoL. (f-50.94) compared to patients with epilepsy disease only (M-57.95), age group patients > 50 years old reported poor HR-QoL (M 45.80) compared to other age groups. Individuals developed epilepsy disease in adolescence appeared to have a higher average HR-QoL score (M-60.22, SD- 14.72), patients who experienced the last seizure epilepsy in more than 6 months (longer intervals) reported better HR-QoL. (M-60.24, SD-13.35) all with (p-value≤ 0.05). Conclusion: The study highlights the poor knowledge and lower HR-Qol. among Omani PWEs Improving understanding about epilepsy leads to better HR-QoL. This emphasizes the need for targeted educational programs and campaigns targeting patients, families and the public to improve knowledge, skills, and HR-QoL for PWEs.