The study aimed to know the frequency and variables associated with COVID-19 vaccine distrust in students of a Colombian university. A cross-sectional study was carried out which participated emerging adult students of a Colombian university. A total of 1,136 students between 18 and 29 years (M= 22.0, SD = 3.0); most of them were female (66.0%), non-health students (82.8%), low-income (79.0%), and residents of urban areas (84.9%). It was frequent low institutional trust (74.8%), low cognitive, social capital (27.9%), low fear of COVID-19 (49.5%), low perceived stress related to COVID-19 (83.5%), and high COVID-19 vaccine distrust (78.9%). Non-health carrier (Adjusted OR = 3.63, 95%CI 2.58-5.10), rural residence (AOR = 1.85, 95%CI 1.13-3.04), low income (AOR = 1.84, 95%CI 1.31-2.57), and perceived stress related to COVID-19 (AOR = 1.74, 95%CI 1.20-2.54) were related to high COVID-19 vaccine distrust. In conclusion, COVID-19 vaccine distrust is high among emerging adult Colombian university students. The COVID-19 vaccine distrust is related to non-health science carriers, rural residents, low-income, and low-perceived stress related to COVID-19. The COVID-19 related health literacy should be improved in students of this university considering socio-cultural background.