As of December 2020, a total of 81 million cases of COVID-19 and nearly 2 million deaths have been reported worldwide. The pandemic is likely to have a major impact on developing countries, putting further pressure on public health systems, which are already overstretched and most likely lack the resources to cope with this pandemic. The pandemic is also demonstrating the unfortunate reality of the health disparities and structural and social inequalities facing people around the world including Spain. Governments have adopted and enacted various policies in response to the pandemic with the goal of mitigating the pandemic and maintaining a healthy economy. These measures, however, have been uneven and heterogeneous, with some countries implementing strict social distancing measures, while others have been slower to enforce mandatory stay-at-home directives for fear of damaging the economy. COVID-19 has impacted people’s lives in multiple areas, including financial stability, education, social connections, academic performance, career development, socioemotional well-being, and health. In addition, the effects of pandemic stress, such as loss of income or work for essential industries such as frontline workers, as well as social isolation and loneliness have increased the risk of alcohol abuse, domestic violence, and mental health problems. Loneliness has the potential to increase alcohol use and mental health problems. Early evidence in this pandemic shows that one-third of adults reported high levels of loneliness during lockdown orders in Spain and the United States. However, no studies in Latin America have measured this variable during the pandemic. Studies examining loneliness, including a systematic review, have found strong and significant associations between social isolation, loneliness and depression, and alcohol consumption in adults and in youth. Therefore, in the context of guidelines on how to prevent COVID-19, more specifically referring to stay-at-home orders, people living alone, or those who feel excluded from their community or people who do not share a sense of identity, it has been shown that risk for alcohol and drug abuse may be increased as well as mental health problems. Alternatively, other studies have shown that social support and living with multiple people is a protective factor against loneliness. Perhaps the same protective factors may benefit people during a pandemic. However, to date, researchers have not evaluated the role of sociocultural factors during the pandemic. Thus, one objective is to assess how sociocultural risk and protective factors affect the relationship between pandemic stress and alcohol use and mental health in college students. Understanding how sociocultural risk and protective factors affect attitudes, beliefs, and behaviors toward COVID-19 mitigation efforts in adults is very important. Sociocultural factors can influence behavior in several ways. For example, individual-level risk factors, such as access to the medical system, and financial stress, may exacerbate the impact of COVID-19. Increasing evidence indicates that loss of income or employment due to the pandemic is associated with higher levels of depressive symptoms, lower levels of self-esteem, higher levels of stress, and higher rates of substance use among adults. In contrast, protective factors at the interpersonal level, including family and social support, have been associated with positive physical and mental health benefits and may be important for COVID-19 mitigation efforts. Adherence to cultural values such as familism, religion, and respect for authority may play an influential role in COVID-19 mitigation behaviors. For example, familism emphasizes maintaining close relationships with the core and family throughout life and has been linked to lower rates of risk behaviors. Similarly, religious values have been found to protect against substance use, and respect for authority may lead to adherence to COVID-19 mitigation guidelines. In this context, it is important to examine attitudes and beliefs toward public health mitigation efforts such as (e.g., social distancing, hand washing, wearing masks) and therapeutic measures, including the use of a vaccine to prevent COVID-19 and how those behaviors may be being driven by sociocultural factors. Moreover, identifying sociocultural risk and protective factors that influence public health practices to reduce COVID-19 risk can inform intervention targets and policy changes to mitigate COVID-19 risk. This study responds to this urgent need by assessing how sociocultural risk and protective factors, along with pandemic stress, influence attitudes, beliefs, and behaviors in adult COVID-19 mitigation efforts in Spain that will allow us to identify commonalities that can inform the development of culturally relevant outreach strategies to mitigate COVID-19 and future epidemics.