The world is facing the COVID-19 pandemic, leading to an unprecedented change in the lifestyle routines of millions. Beyond the general physical health, financial, and social repercussions of the pandemic, the adopted mitigation measures also present significant challenges in the population’s mental health and health programs. It is complex for public organizations to measure the population’s mental health in order to incorporate it into their own decision-making process. Traditional survey methods are time-consuming, expensive, and fail to provide the continuous information needed to respond to the rapidly evolving effects of governmental policies on the population’s mental health. A significant portion of the population has turned to social media to express the details of their daily life, rendering this public data a rich field for understanding emotional and mental well-being. This study aims to track and measure the sentiment changes of the Mexican population in response to the COVID-19 pandemic. To this end, we analyzed 760,064,879 public domain tweets collected from a public access repository to examine the collective shifts in the general mood about the pandemic evolution, news cycles, and governmental policies using open sentiment analysis tools. Sentiment analysis polarity scores, which oscillate around -0.15, show a weekly seasonality according to Twitter’s usage and a consistently negative outlook from the population. It also remarks on the increased controversy after the governmental decision to terminate the lockdown and the celebrated holidays, which encouraged the people to incur social gatherings. These findings expose the adverse emotional effects of the ongoing pandemic while showing an increase in social media usage rates of 2.38 times, which users employ as a coping mechanism to mitigate the feelings of isolation related to long-term social distancing. The findings have important implications in the mental health infrastructure for ongoing mitigation efforts and feedback on the perception of policies and other measures. The overall trend of the sentiment polarity is 0.0001110643.