The objective of this narrative review is to analyze the impact of COVID-19 on the mental health of particularly vulnerable groups. This information will allow a better understanding of the determining factors that influence the appearance and/or maintenance of mood disorders. To achieve the main objective of this study, a critical review was carried out in which primary sources such as scientific articles, secondary sources such as databases, and other appropriate reference indexes were considered. The results indicated that there was an increase in the diagnosis of mood disorders and the use of medication associated with these disorders, mainly during the period of reclusion that was declared worldwide in March 2020. In addition, risk factors such as loneliness, a lack of resilience, and a lack of adequate coping strategies negatively impacted these groups. The future consequences of this may be reflected over many years thereafter, and it is important that all data obtained from this point forward be considered by mental health professionals and the general population. This review can be a starting point for looking directly at the most vulnerable populations and considering both the resources available to them and the possible aftermath of a traumatic period in everyone’s lives.