The COVID-19 pandemic has represented a new form of trauma, being a completely unexpected event, affecting the whole population worldwide, and causing severe disruption of daily life. The pandemic and its related containment measures have had a serious negative impact on the mental health of the general population and of special target groups. The COVID-19 contagion, the lockdown, and the restrictive measures adopted by the national government have had a detrimental impact on specific target populations including people with preexisting mental disorders and healthcare workers. Individuals with preexisting mental disorders reported a high risk of experiencing a clinical relapse and were at higher risk of developing significant anxiety, depressive, and stress symptoms, as well as experiencing sleep disorders. The COVID-19 pandemic has represented an unprecedented traumatic event, for which healthcare professionals were not adequately equipped to manage but have been able to promptly reorganize healthcare services and the types of interventions offered in order to contain its detrimental impact on mental health. Recognizing and understanding the different pathways underlying the detrimental impact of the pandemic is essential for developing tailored mental health interventions and promoting best practices in healthcare services.