Cultural self-efficacy refers to how capable one feels functioning in culturally diverse situations. The purpose of this study was to gain a better understanding of cultural self-efficacy among nursing students, specifically in relation to individuals of Aboriginal ancestry. The authors examined the extent to which intercultural anxiety, intercultural communication, and experience with persons of Aboriginal ancestry predicted two aspects of cultural self-efficacy, namely, knowledge and skills. In this correlational study, non-Aboriginal Canadian nursing students (N = 59) completed a survey assessing these variables. Overall, cultural self-efficacy was rated as moderate by nursing students. Regression analyses indicated that greater intercultural communication skills and experience with persons of Aboriginal ancestry were significant unique predictors of higher cultural knowledge self-efficacy. Greater intercultural communication and lower intercultural anxiety significantly predicted higher cultural skills self-efficacy. The results provide direction to nursing programs interested in facilitating higher levels of cultural self-efficacy among nursing students.