Objective: The aim of this study was to determine the association among temperature, relative humidity, latitude, vitamin D content and comorbidities in the spread of SAR-CoV-2 in Mexico in 2 different waves. Methods: The data on SARS-CoV-2 infections and comorbidities were obtained from the Mexican entities with the highest number of positive cases and deaths in the 2 waves that have most damaged the population. Results: Low temperature, high relative humidity, vitamin D deficiency and high percentage of comorbidities were factors that correlated with a high spread of SARS-CoV-2. Interestingly, 73.8% of the population had one of the most common comorbidities that favor the spread of the virus. Conclusion: The high percentage of comorbidities and the deficient concentration of vitamin D were determining factors in the high number of infections and deaths in Mexico. Furthermore, weather conditions could contribute to and alert to the spread of SARS-CoV-2.