2020 broke records for the most active fire year on the West Coast, resulting in the worst air quality observed in decades. Concurrently, the public health threat of COVID-19 caused over 1 million deaths in the United States (US) and Mexico in 2020 and 2021. Due to the effect of air pollution on respiratory diseases, wildfire-specific particulate matter is a hypothesized driver of COVID-19 severity and death. Capitalizing on wildfire smoke that hit the San Diego-Tijuana border region in September 2020, we applied synthetic control methods to explore its differential role in affecting COVID-19 mortality on both sides of the border. Daily data on COVID-19 cumulative deaths for US Counties was obtained from the CDC COVID tracker and data for Mexican Municipalities was obtained from the Mexican Secretary of Health. Counties and Municipalities with wildfire smoke exposure were identified using the NOAA hazard mapping Smoke Product; a day where 90% of the area covered by smoke was considered exposed for the main analyses. Unexposed Counties/Municipalities were considered as potential controls. The San Diego-Tijuana border region was covered by dense smoke by September 7th; 707 COVID-19 deaths had occurred in San Diego and 1367 in Tijuana. While a slight increase in cumulative mortality was observed in San Diego, no change was found in Tijuana; neither estimate indicated a strong precise effect of wildfire smoke on COVID-19 mortality. We hope this study will serve as an illustration of how border contexts can be used to investigate differential vulnerability to wildfire smoke for infectious diseases. Examining the interactive effect of COVID-19 and smoke can help in recognizing the implications of these dual health risks which will be increasingly important as wildfires become more frequent and severe in the context of climate change.