This study examines how social determinants associated with COVID-19 mortality change over time. Using US county-level data from July 5 and December 28, 2020, the effect of 19 high-risk factors on COVID-19 mortality rate was quantified at each time point with negative binomial mixed models. Then, these high-risk factors were used as controls in two association studies between 40 social determinants and COVID-19 mortality rates using data from the same time points. The results indicate that counties with certain ethnic minorities and age groups, immigrants, prevalence of diseases like pediatric asthma and diabetes and cardiovascular disease, socioeconomic inequalities, and higher social association are associated with increased COVID-19 mortality rates. Meanwhile, more mental health providers, access to exercise, higher income, chronic lung disease in adults, suicide, and excessive drinking are associated with decreased mortality. Our temporal analysis also reveals a possible decreasing impact of socioeconomic disadvantage and air quality, and an increasing effect of factors like age, which suggests that public health policies may have been effective in protecting disadvantaged populations over time or that analysis utilizing earlier data may have exaggerated certain effects. Overall, we continue to recognize that social inequality still places disadvantaged groups at risk, and we identify possible relationships between lung disease, mental health, and COVID-19 that need to be explored on a clinical level.