The COVID-19 epidemic has caused higher education institutions in Vietnam to immediately transfer from traditional classrooms to e-learning environments. This interacts with high expectations and habits of learning and training can adversely affect the mental health of students. The purpose of this study is to validate the DASS-21 scale for use in the mental health screening in Vietnamese students when they suffer an immediate psychological reaction in the e-learning environment. Strict statistical analyzes (including Cronbach's alpha, Exploratory Factor Analysis, Confirmatory Factor Analysis, Average Variance Extracted, Average Shared Variance) have led to a well-fitting model of DASS-18 with a three-factor structure to measure the mental health of Vietnamese students in an e-learning environment. Results DASS-18 reported the rates of depression, anxiety, and stress in levels of moderate severity or above in Vietnamese students at 50%, 19.7%, and 37.3%, respectively. However, a rate of anxiety up to 43.1% by using DASS-21 indicating that many students may be misdiagnosed for the level of anxiety. Finally, linear regression analyses are used to examine the influence of socio-demographic factors on the immediate psychological responses of students to an e-learning environment in the context of the COVID-19 epidemic.