To provide high-quality nursing care, nursing education requires the basic quality of self-leadership from professional nurses so that they can make self-directed and responsible judgments and decisions. Therefore, this study aimed to investigate relationships among self-leadership, positive psychological capital, consciousness of calling, and nursing professionalism in nursing students. A cross-sectional online survey of 202 students from two universities in South Korea was conducted between August and September 2022, using a convenience sampling method. A structured questionnaire was used to collect data. Data were analyzed using descriptive statistics, Pearson’s correlation coefficient analysis, and bootstrapping using Hayes’ PROCESS macro for mediation. A significant positive correlation was found between self-leadership, positive psychological capital, consciousness of calling, and nursing professionalism. Positive psychological capital and consciousness of calling showed an indirect mediating effect on the relationship between self-leadership and nursing professionalism. To improve nursing professionalism, programs should be developed to educate nursing students, strengthen their self-leadership skills, and increase the influence of positive psychological capital and consciousness of calling for nursing. This will ultimately contribute to improving the quality of patient care by fostering competent nursing experts.