BACKGROUND: Climate change will increase drought duration and severity in many regions around the world, including the Central Plains of North America. However, studies on drought-related health impacts are still sparse. This study aims to explore the potential associations between drought and all-cause mortality in Nebraska from 1980 to 2014. METHODS: The Evaporative Demand Drought Index (EDDI) were used to define short-, medium- and long-term drought exposures, respectively. We used a Bayesian zero-inflated censored negative binomial (ZICNB) regression model to estimate the overall association between drought and annual mortality first in the total population and second in stratified sub-populations based on age, race, sex, and the urbanicity class of the counties. RESULTS: The main findings indicate that there is a slightly negative association between all-cause mortality and all types of droughts in the total population, though the effect is statistically null. The joint-stratified analysis renders significant results for a few sub-groups. White population aged 25-34 and 45-64 in metro counties and 45-54 in non-metro counties were the population more at risk in Nebraska. No positive associations were observed in any race besides white. Black males aged 20-24 and white females older than 85 showed protective effect against drought mainly in metro counties. We also found that more sub-populations had higher rates of mortality with longer-term droughts compared to shorter-term droughts (12-month vs 1- or 6-month timescales), in both metro and non-metro counties, collectively. CONCLUSION: Our results suggest that mortality in middle aged white population in Nebraska shows a greater association with drought. Moreover, women aged 45-54 were more affected than men in non-metro counties. With a projected increase in the frequency and severity of drought due to climate change, understanding these relationships between drought and human health will better inform drought mitigation planning to reduce potential impacts.