The COVID-19 pandemic has exacerbated the risk of opioid-related harm, and previous studies suggest a connection between opioid overdose risk and industry of employment. We used descriptive and spatial-statistical tests with opioid overdose data from the vital records offices of Kentucky and Massachusetts to examine opioid overdose rates by employment industry before and after COVID-19 emergency declarations. Both states had consistently high rates of opioid-related overdose mortality for individuals employed in the construction and arts, recreation, food services, and accommodation service industries. Additionally in both states, census tracts with a high percentage of renters and non-Hispanic Black residents were more likely to be located in fatal opioid-related overdose hotspots following the initial surge of COVID-19 cases. In Kentucky, census tracts with higher percentages of employment in the transportation and other services were more likely to be located in an overdose hotspot before and after the COVID-19 emergency declaration, while in Massachusetts the same was true for census tracts with high employment in manufacturing, agriculture, forest, and fisheries, and hunting.