<b><i>Background:</i></b> During the COVID-19 pandemic, a decrease in well-being and an increase in mental health problems were registered in medical and psychotherapeutic practices, counseling centers, and clinics. According to previous studies, younger people and women seemed to be particularly affected. The aim of this study was to describe mental health problems of students and to draw consequences for the further handling of pandemics and other crises. <b><i>Method:</i></b> Students at the University of Heidelberg, a typical German “full university,” were surveyed online using internationally comparable screening instruments like the Well-Being Index (WHO-5) and the Patient Health Questionnaire (PHQ). In addition, the students had the opportunity to describe in a narrative form their well-being and to make suggestions how to improve their situation. <b><i>Results:</i></b> Out of a population of 27,162 students who were contacted by email, 2,137 students completed the questionnaire. The salient finding is that according to the WHO-5 Well-Being Index, 72.2% of the respondents feel seriously impaired in their well-being. This corresponds to the finding that 75.8% of the respondents in the PHQ-D show indications of at least one syndrome diagnosis. Depression was found in 41.8% of the respondents in the PHQ-D. Indications of moderate to severe and severe depressive syndromes were present in 31.8%. Signs of somatoform syndromes are found in 25.4% and of anxiety syndromes in 20.0%. 1,089 students gave narrative reports on how they were feeling and made suggestions for improvement. About 75% reported severely reduced well-being. Their main complaints were loneliness and depression and lack of recognition for their specific academic and life situation during the pandemic. By far, the largest proportion of students supposed that their mental health issues were caused and/or intensified by the pandemic-related social contact restrictions. The vast majority of them made reasonable suggestions for controlled relaxation of contact restrictions. <b><i>Conclusions:</i></b> Students suffer severely from the pandemic-related social restriction. In respect to future pandemic outbreaks or other crises leading to social isolation, the dramatic consequences of social lockdowns should be taken into account. Under pandemic conditions, we especially should support persons lacking social networks.