Abstract: Since the outbreak of Coronavirus disease (COVID-19) in late 2019, it has become a global pandemic, with severe impact on health and economy. The increasing prevalence of COVID-19 cases and the deaths in the United States (US) indicates a lack of compliance with the national and state guidelines by the Centers for Disease Control and Prevention (CDC). Mississippi (MS) has one of the highest number of cases and deaths than the national U.S average. This study reveals the risks and burden of COVID-19 in MS when compared to the US national average and proposes strict preventive measures to reduce the spread of Covid-19 in the state of Mississippi. This could be achieved through social distancing, use of face coverings, proper hand hygiene, virtual learning, decentralized contact tracing, and a probable second lockdown.