Objective: This paper examines the contributions made by the National Institute of Public Health to Cambodia’s response to the coronavirus disease (COVID-19) pandemic during 2020–2021. Methods: The activities conducted by the Institute were compared with adaptations of the nine pillars of the World Health Organization’s 2020 COVID-19 strategic preparedness and response plan. To gather relevant evidence, we reviewed national COVID-19 testing data, information about COVID-19-related events documented by Institute staff, and financial and technical reports of the Institute’s activities. Results: The main contributions the Institute made were to the laboratory pillar and the incident management and planning pillar. The Institute tested more than 50% of the 2 575 391 samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and provided technical advice about establishing 18 new laboratories for SARS-CoV-2 testing in the capital city of Phnom Penh and 11 provinces. The Institute had representatives on many national committees and coauthored national guidelines for implementing rapid COVID-19 testing, preventing transmission in health-care facilities and providing treatment. The Institute contributed to six other pillars, but had no active role in risk communication and community engagement. Discussion: The Institute’s support was essential to the COVID-19 response in Cambodia, especially for laboratory services and incident management and planning. Based on the contributions made by the Institute during the COVID-19 pandemic, continued investment in it will be critical to allow it to support responses to future health emergencies in Cambodia.