Background: During the COVID-19 pandemic, the Uruguayan government decided to call for an attitude of responsible freedom of the population and created an Honorary Scientific Advisory Group (GACH). The intention was to report the scientific evidence available on the health situation with transparency and technical independence and to recommended interventions. This paper aims (1) to analyze the strategy to combat the COVID-19 pandemic used in Uruguay from the perspective and principles of person-centered medicine (PCM), (2) to report and examine from a broad perspective the policy regarding health authorities, scientific evidence and population, and (3) to discuss the importance of mental health and behavioral monitoring for identifying vulnerable groups that require special attention and care. Methods: Retrospective and narrative analysis of the creation of a socioeconomic and behavioral observatory [OSEC], critical evaluation of key data collection on population mental health, and assessment of the influence of OSEC in the context of the pandemic in Uruguay. T-test was used to assess mean differences of mental health trends in the general population using GHQ-12 panel data. The article presents the results obtained on the country’s mental health data through the analysis of a helpline consultations and a digital panel survey of a representative sample of the Uruguayan population. Screening instruments were used, which allowed for an identification of risk groups. Results: The evidence shows the impact of the pandemic on the emotional distress of the population, indicating that the population discomfort decreased significantly when the pandemic situation began to improve. In addition, differences according to socioeconomic status and age groups were observed, showing that the most disadvantaged had significantly higher levels of emotional distress than those of the middle and upper class, at all times of analysis. Conclusions: Apparently, it is possible to extend the principles of beneficence, autonomy, and justice applied at the individual level to the level of collective health policies. This is essential to achieve the active participation of the population in their self-care and to promote greater and more transparent communication with the health and scientific fields. It is also necessary to adopt a holistic, biopsychosocial perspective, which makes it possible to identify the vulnerable sectors of society and the areas in which special attention is required.