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Background and aims The COVID-19 health crisis has created a disastrous situation worldwide. All nations are facing this pandemic, including eastern Mediterranean countries. The aim of this study is to assess and compare the impact of this devastating pandemic on lower-middle-income countries in the eastern Mediterranean region, identify the leading causes of its spread, examine the various risk factors associated with its virulence in each country, and provide effective intervention strategies to contain it. Methods Using the analysis of variance method, this research compares infection, case fatality, recovery, and positivity rates in seven countries, namely, Morocco, Tunisia, Egypt, Djibouti, Pakistan, Sudan, and Palestine. It focuses on their daily reported confirmed incidents, recoveries, deaths, and tests. Results The results highlight the significant differences in the effect of COVID-19 in these countries. Regarding the infection rate, Djibouti and Palestine have the highest rate, which could be related to the high poverty and the young population in these countries. However, it has been demonstrated that Tunisia, Djibouti, Egypt, and Sudan have the greatest case fatality rate in this comparison, which might be attributed to the relatively old population in Tunisia, the co-morbidity in Egypt, and the deficiency of the healthcare system in Djibouti and Sudan. Furthermore, the comparison of the recovery rate in these countries indicates that Djibouti has the highest recovery rate, which might be due to the young population. Conclusion This work allows us to come up with recommendations that could support policymakers to act efficiently in containing the pandemic flare-up.