Background: COVID-19 is a significant public health problem that can have a negative impact, especially in vulnerable regions. Objective: This study aimed to provide evidence that could positively influence coping with COVID-19 based on the relationship between the potential epidemic vulnerability index (PEVI) and socioepidemiological variables. This could be used as a decision-making tool for the planning of preventive initiatives in regions with relevant vulnerability indices for the spread of SARS-CoV-2. Methodology: We performed a cross-sectional study, with the analysis of the population characteristics of COVID-19 cases associated with neighborhoods’ PEVIs in the conurbation region of Crajubar, northeastern Brazil, through the mapping of socioeconomic–demographic factors and spatial autocorrelation. Results: The PEVI distribution indicated low vulnerability in areas with high real estate and commercial value; as communities moved away from these areas, the vulnerability levels increased. As for the number of cases, three of the five neighborhoods with a high–high autocorrelation, and some other neighborhoods showed a bivariate spatial correlation with a low–low PEVI but also high–low with indicators that make up the PEVI, representing areas that could be protected by public health measures to prevent increases in COVID-19 cases. Conclusions: The impact of the PEVI revealed areas that could be targeted by public policies to decrease the occurrence of COVID-19.