This study investigated the differences between Chinese female and male university students regarding the relationship between conscientiousness, interpersonal relationships, and social loafing. By analyzing these relationships, this study interpreted how personality, mediators, and gender differences affect social loafing. In total, 827 Chinese university students were recruited from three universities in Xi'an, Shaanxi, China. Students completed an online questionnaire, which included a conscientiousness scale, an interpersonal relationship scale, and a social loafing scale. Structural equation modeling was performed to test the validity of the measurement scales, mediating effects, and group differences. The findings revealed that the relationship between conscientiousness, interpersonal relationships, and social loafing differed between female and male Chinese university students. Interpersonal relationships served as a partial mediator in the relationship between conscientiousness and social loafing among female students. Interpersonal relationships did not play a mediating role in the relationship between conscientiousness and social loafing among male students. We suggest that university administrators should promote cooperation among Chinese university students.