The SARS-CoV-2 virus pandemic has forced far-reaching changes in higher education. Isolation from peers and distance learning have significantly limited interpersonal contacts, which might have affected the mental well-being of students. Therefore, the aim of the study was to investigate the prevalence of depressive symptoms and the level of perceived stress during e-learning among Slovak students and to identify the variables that have the most significant impact on mental health among students. The study included 3051 participants, 1773 women (58%) and 1278 (42%) with a mean age of 22.37 years. The Perceived Stress Scale (PSS-10) and Beck Depression Inventory (BDI-II) were used to measure the severity of stress and depression level. In addition, an author's survey was used assessing the areas of social life, education skills, economic field, nutrition habits, and drugs. Almost all study participants were characterized by increased stress level and 47% of them were depressed. Moreover, isolation affected women more, especially in terms of social life and economics. It seems necessary to implement appropriate support programs for students, which could have the potential to improve their psychological condition.