The global health security (GHS) Index assesses countries’ level of preparedness to health risks. However, there is no evidence on how and whether the effects of health systems building blocks and socioeconomic indicators on the level of preparedness differ for low and high prepared countries. The aim of this study was to examine the contributions of health systems building blocks and socioeconomic indicators to show differences in the level of preparedness to health risks. The study also aimed to examine trends in the level of preparedness and the World Health Organization (WHO) regional differences before and during the Covid-19 pandemic. We used the 2021 GHS index report data and employed quantile regression, log-linear, double-logarithmic, and time-fixed effects models. As robustness checks, these functional form specifications corroborated with one another, and interval validity tests confirmed. The results show that increases in effective governance, supply chain capacity in terms of medicines and technologies, and health financing had positive effects on countries’ level of preparedness to health risks. These effects were considerably larger for countries with higher levels of preparedness to health risks. The positive gradient trends signaled a sense of capacity on the part of countries with higher global health security. However, the health workforce including doctors, and health services including hospital beds, were not statistically significant in explaining variations in countries’ level of preparedness. While economic factors had positive effects on the level of preparedness to health risks, their impacts across the distribution of countries’ level of preparedness to health risks were mixed. The effects of Social Development Goals (SDGs) were greater for countries with higher levels of preparedness to health risks. The effect of the Human Development Index (HDI) was greatest for countries whose overall GHS index lies at the midpoint of the distribution of countries’ level of preparedness. High-income levels were associated with a negative effect on the level of preparedness, especially if countries were in the lower quantiles across the distributions of preparedness. Relative to poor countries, middle- and high-income groups had lower levels of preparedness to health risks, an indication of a sense of complacency. We find the pandemic period (year 2021) was associated with a decrease in the level of preparedness to health risks in comparison to the pre-pandemic period. There were significant WHO regional differences. Apart from the Eastern Mediterranean, the rest of the regions were more prepared to health risks compared to Africa. There was a negative trend in the level of preparedness to health risks from 2019 to 2021 although regional differences in changes over time were not statistically significant. In conclusion, attempts to strengthen countries’ level of preparedness to health shocks should be more focused on enhancing essentials such as supply chain capacity in terms of medicines and technologies; health financing, and communication infrastructure. Countries should also strengthen their already existing health workforce and health services. Together, strengthening these health systems essentials will be beneficial to less prepared countries where their impact we find to be weaker. Similarly, boosting SDGs, particularly health-related sub-scales, will be helpful to less prepared countries. Moreover, there is a need to curb complacency in preparedness to health risks during pandemics by high-income countries. The negative trend in the level of preparedness to health risks would suggest that there is a need for better preparedness during pandemics by conflating national health with global health risks. This will ensure the imperative of having a synergistic response to global health risks, which is understood by and communicated to all countries and regions.