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<b>Introduction:</b> The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made COVID-19 one of the biggest pandemics of all time, with several devastating public health challenges. In this study, we investigated the knowledge towards COVID-19 best practices in the north of Portugal. <b>Methods:</b> A descriptive cross-sectional study was performed with a convenience sample of the population of northern Portugal to assess their knowledge about COVID-19, SARS-CoV-2 and measures to prevent and mitigate pandemics. An online validated questionnaire was completed by 411 participants, from September to October 2020. <b>Results:</b> The overall correct knowledge was 81.3%, which indicates a good knowledge by the northern Portuguese respondents about COVID-19. The correct answer score differed considerably between men and women, being significantly higher among the latter (12.28 ± 1.22; <i>p</i> = 0.011). Moreover, the highest knowledge was observed in participants who attended high school or above (12.27 ± 1.21; <i>p</i> < 0.000). <b>Conclusion:</b> This study contributes to the analysis of COVID-19 knowledge by the northern Portuguese population, emphasizes the crucial role of health education in the control and mitigation of the COVID-19 pandemic, and provides field-based evidence to prevent the next pandemic event.