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Non-Pharmaceutical Public Health Interventions (NPHIs) have been used by different countries to control the spread of the COVID-19. Despite available evidence regarding the effectiveness of NPHSs, there is still no consensus about how policymakers can trust these results. Studies on the effectiveness of NPHSs are single studies conducted in specific communities. Therefore, they cannot individually prove if these interventions have been effective in reducing the spread of the infection and its adverse health outcomes. In this systematic review, we aimed to examine the effects of NPHIs on the COVID-19 case growth rate, death growth rate, Intensive Care Unit (ICU) admission, and reproduction number in countries, where NPHIs have been implemented. We searched relevant electronic databases, including Medline (via PubMed), Scopus, CINAHL, Web of Science, etc. from late December 2019 to February 1, 2021. The key terms were primarily drawn from Medical Subject Heading (MeSh and Emtree), literature review, and opinions of experts. Peer-reviewed quasi-experimental studies were included in the review. The PROSPERO registration number is CRD42020186855. Interventions were NPHIs categorized as lockdown, stay-at-home orders, social distancing, and other interventions (mask-wearing, contact tracing, and school closure). We used PRISMA 2020 guidance for abstracting the data and used Cochrane Effective Practice and Organization of Practice (EPOC) Risk of Bias Tool for quality appraisal of the studies. Hartung-Knapp-Sidik-Jonkman random-effects model was performed. Main outcomes included COVID-19 case growth rate (percentage daily changes), COVID-19 mortality growth rate (percentage daily changes), COVID-19 ICU admission (percentage daily changes), and COVID-19 reproduction number changes. Our search strategies in major databases yielded 12,523 results, which decreased to 7,540 articles after eliminating duplicates. Finally, 35 articles qualified to be included in the systematic review among which 23 studies were included in the meta-analysis. Although studies were from both low-income and high-income countries, the majority of them were from the United States (13 studies) and China (five studies). Results of the meta-analysis showed that adoption of NPHIs has resulted in a 4.68% (95% CI, -6.94 to -2.78) decrease in daily case growth rates, 4.8% (95 CI, -8.34 to -1.40) decrease in daily death growth rates, 1.90 (95% CI, -2.23 to -1.58) decrease in the COVID-19 reproduction number, and 16.5% (95% CI, -19.68 to -13.32) decrease in COVID-19 daily ICU admission. A few studies showed that, early enforcement of lockdown, when the incidence rate is not high, contributed to a shorter duration of lockdown and a lower increase of the case growth rate in the post-lockdown era. The majority of NPHIs had positive effects on restraining the COVID-19 spread. With the problems that remain regarding universal access to vaccines and their effectiveness and considering the drastic impact of the nationwide lockdown and other harsh restrictions on the economy and people's life, such interventions should be mitigated by adopting other NPHIs such as mass mask-wearing, patient/suspected case isolation strategies, and contact tracing. Studies need to address the impact of NPHIs on the population's other health problems than COVID-19.