Following the COVID-19 outbreak, psychological stress was particularly pronounced in the student population due to prolonged home isolation, online study, closed management, graduation, and employment pressures. The objective of this study is to identify the incidence of psychological stress reactions in student populations following a global outbreak and the associated influencing factors. Four English databases (Pubmed, Embase, Cochrane Library, Web of Science) and four Chinese biomedical databases (Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, Wanfang) were searched in this study. We also retrieved other search engines manually. The search period was from the time of database creation to 10 March 2022. This study included cross-sectional studies related to psychological stress reactions in student populations during the COVID-19 epidemic. Three groups of researchers screened the retrieved studies and assessed the quality of the included studies using the Agency for Healthcare Research and Quality Cross-Sectional Study Quality Assessment Checklist. A random-effects model was used to analyze the prevalence of depression, anxiety, stress, and fear symptoms in the student population during the COVID-19 epidemic. Of the 146,330 records retrieved, we included 104 studies (n = 2,088,032). The quality of included studies was moderate. The prevalence of depressive symptoms in the student population during the epidemic was 32.0% (95% CI [28.0–37.0%]); anxiety symptoms was 28.0% (95% CI [24.0–32.0%]); stress symptoms was 31.0% (95% CI [23.0–39.0%]); and fear symptoms was 33.0% (95% CI [20.0–49.0%]). The prevalence differed by gender, epidemic stage, region, education stage, student major and assessment tool. The prevalence of psychological stress in the student population during the COVID-19 epidemic may be higher compared to the global prevalence of psychological stress. We need to alleviate psychological stress in the student population in a targeted manner to provide mental health services to safeguard the student population.