Background: Cultural intelligence has been described as an essential intelligence for the 21st century that can increase students' adaptability, problem-solving skills, and influence their performance and learning vitality. Aim of this study was to investigate the relationship between cultural intelligence and academic vitality with selfdirected learning among nursing students. Design: Descriptive, correlational study design was adopted. Setting:The study was conducted at Faculty of Nursing, Tanta University. Subjects: All fourth year nursing students (n=295) were included. Tools: Three tools for data collection were used to achieve the aim of this study; Cultural Intelligence Scale, Academic Vitality Questionnaire and Self-Directed Learning Instrument (SDLI). Results: As a result of the conducted study revealed that there is a high level of culture intelligence and academic vitality with moderate level of self-directed learning among nursing students. There were significant positive correlation between self-directed learning (r= 0.33) and its aspects including, self-management (r= 0.72), desire for learning (r= 0.58) and self-monitoring (r=0.52) with cultural intelligence and academic vitality (P<0.01). Conclusion: Selfdirected learning seems to be a phenomenon that is influenced by many factors such as cultural intelligence and academic vitality. Recommendations: this study suggests that academic vitality and culture intelligence should be considered together when self-directed learning is conducted to improve nursing students' academic performance. Workshops should be held in order to promote self-directed learning among students.